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Information on EC 4.2.99.18 - DNA-(apurinic or apyrimidinic site) lyase and Organism(s) Homo sapiens and UniProt Accession P27695
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4.2.99.18 DNA-(apurinic or apyrimidinic site) lyaseIUBMB Comments
'Nicking' of the phosphodiester bond is due to a lyase-type reaction, not hydrolysis. This group of enzymes was previously listed as endonucleases, under EC 3.1.25.2.
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Word Map
- 4.2.99.18
- strand
-
exonuclease
- glycosylases
-
single-stranded
- pyrimidine
- endonucleases
- 8-oxoguanine
- nick
- thymine
- uracil
- duplex
-
genotoxic
- xrcc1
-
phosphodiester
- comet
- deoxyribose
- methanesulfonate
- mispairs
-
uracil-dna
-
depurinated
-
beta-elimination
-
excise
- formamidopyrimidine
-
3'-phosphatase
- 7,8-dihydro-8-oxoguanine
- tetrahydrofuran
-
site-containing
-
mutyh
-
endonucleolytic
-
xeroderma
- pigmentosum
-
base-excision
- 3'-phosphodiesterase
-
cross-complementing
- 8-oxo-7,8-dihydroguanine
- fen1
-
unrepaired
-
formamidopyrimidine-dna
-
incises
-
long-patch
-
dna-repair
-
uracil-containing
-
ser326cys
- dihydrouracil
-
arg399gln
- 3'-exonuclease
-
reduction-oxidation
-
enzyme-dna
- medicine
-
gap-filling
-
damage-specific
- analysis
- diagnostics
- biotechnology
- drug development
- pharmacology
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate
Synonyms
ap endonuclease, ref-1, ape1/ref-1, apex1, ape/ref-1, apurinic/apyrimidinic endonuclease 1, ap lyase, ape-1, alkbh1, endo iii, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
APE1
-
apurinic/apyrimidic endonuclease 1
member of the divalent cation-dependent phosphoesterase superfamily of proteins
apurinic/apyrimidinic endonuclease
-
apurinic/apyrimidinic endonuclease 1
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AP 1
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-
-
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AP Dnase
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-
-
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AP endo
AP endonuclease
AP endonuclease Class I
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-
-
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AP lyase
AP-endonuclease
Ape
APE1
APEN
-
-
-
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APEX nuclease
-
-
-
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APN1
-
-
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apurinic DNA endonuclease
-
-
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apurinic endodeoxyribonuclease
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-
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apurinic endonuclease
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-
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apurinic endonuclease 1
apurinic-apyrimidinic DNA endonuclease
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-
-
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apurinic-apyrimidinic endodeoxyribonuclease
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-
-
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apurinic-apyrimidinic endonuclease
-
-
-
-
apurinic/apyrimidinic endonuclease
-
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apurinic/apyrimidinic endonuclease 1
-
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apurinic/apyrimidinic lyase
-
-
-
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apurinic/apyrimidinic specific endonuclease
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-
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apyrimidinic endonuclease
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-
-
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class II apurinic/apyrimidinic(AP)-endonuclease
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-
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deoxyribonuclease (apurinic or apyrimidinic)
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-
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E. coli endonuclease III
-
-
-
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endodeoxyribonuclease
-
-
-
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endodeoxyribonuclease III
-
-
-
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endonuclease III
endonuclease VI
-
-
-
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Escherichia coli endonuclease III
-
-
-
-
HAP1
HAP1h
-
-
-
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Micrococcus luteus UV endonuclease
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-
-
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MMH
-
-
-
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Nfo
-
-
-
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Ntg1p
-
-
-
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Ntg2p
-
-
-
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NTH1
-
-
-
-
nuclease, apurinic endodeoxyribo-
-
-
-
-
nuclease, apurinic-apyrimidinic endodeoxyribo-
-
-
-
-
nuclease, endodeoxyribo-, III
-
-
-
-
phage-T4 UV endonuclease
-
-
-
-
REF-1 protein
-
-
-
-
Ref1
UV endo V
-
-
-
-
UV endonuclease
-
-
-
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UV endonuclease V
-
-
-
-
additional information
-
Ku is a NHEJ factors with effective 5'-deoxyribose-5-phosphate lyase/apurinic/apyrimidinic site lyase activities
AP endo
-
-
-
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AP endonuclease
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-
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AP lyase
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-
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AP-endonuclease
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-
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Ape
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-
-
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APE1
-
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endonuclease III
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-
-
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HAP1
-
-
-
-
Ref1
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate
mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
endonuclease reaction
endonuclease reaction
additional information
-
APE1 possesses endonuclease, exonuclease and phosphodiesterase activity
endonuclease reaction
an essential protein that functions as part of base excision repair to remove mutagenic and cytotoxic abasic sites from DNA
endonuclease reaction
-
-
endonuclease reaction
-
the protein has AP endonuclease and 3'-5' exonuclease activity
SYSTEMATIC NAME
IUBMB Comments
DNA-(apurinic or apyrimidinic site) 5'-phosphomonoester-lyase
'Nicking' of the phosphodiester bond is due to a lyase-type reaction, not hydrolysis. This group of enzymes was previously listed as endonucleases, under EC 3.1.25.2.
CAS REGISTRY NUMBER
COMMENTARY
60184-90-9
-
61811-29-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
43-mer oligonucleotide containing apurinic/apyrimidinic sites
fragments of DNA
-
-
-
?
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
?
a synthetic stable AP-site analog where X represents tetrahydrofuran
-
-
?
AP-DNA
fragments of DNA
Base excision repair pathway, enzyme cleaves the 5'-phosphodiester bond, generating 3'-OH and 5'-dRP termini
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
hydrogen bonds to phosphate groups 3' to the cleavage site is essential for the binding of the enzyme to the product DNA, which may be necessary for efficient functioning of the base excision rapair pathway
-
-
?
12-mer oligodeoxyribonucleotide containing a 2'-deoxyguanosine at the natural AP site
?
-
-
-
-
?
12-mer oligodeoxyribonucleotide containing a natural AP site
?
-
the minimal kinetic model for the natural AP site incision consists of four stages corresponding to three different transient states of APE1. When the enzyme is complexed with the AP-substrate, the catalytic cycle is completed within 3 s
-
-
?
12-mer oligodeoxyribonucleotide containing a tetrahydrofuran analogue at the natural AP site
?
-
-
-
-
?
3'-fluorescein-labeled 5'-AACTTCGTGCAGGCATGGTAG(dU)TTGTCTACT-3'
?
-
-
-
?
43-mer oligonucleotide containing the AP-site analog tetrahydrofuran at nt 31
?
-
-
-
-
?
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
?
-
the fluorogenic substrate OligoI is based on the sequence immediately surrounding the stem V-loop region (OligoI) and incorporating a fluorescent tag, Cy3, at the 5' end and a fluorescence Black Hole Quencher at the 3' end of the oligonucleotide
-
-
?
5'-Cy3-CAAGGTAGTTATCCTTG-1-Black Hole Quencher1-3'
?
-
the fluorogenic substrate DNAOligoI is based on the sequence immediately surrounding the stem Vloop region (OligoI) and incorporating a fluorescent tag, Cy3, at the 5' end and a fluorescence Black Hole Quencher at the 3' end of the oligonucleotide, DNAOligoI has an identical sequence to OligoI except that deoxythymidylate is substituted for 2' hydroxyl uridine
-
-
?
AP-DNA-RNA
?
-
synthetic DNA-RNA hybrids that simulate a transcription intermediate
-
-
?
c-myc coding region determinant mRNA
?
-
APE1 preferentially cleaves in between UA and CA dinucleotides of c-myc coding region determinant RNA
-
-
?
c-myc RNA
?
-
APE1 cleaves at the UA, CA, and UG sites of c-myc RNA in vitro
-
-
?
DNA containing tamdem dihydrouracil
?
-
the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
-
-
?
DNA containing tandem dihydrouracil
?
-
the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
-
-
?
duplex oligonucleotide containing a 5,6-dihydro-2'-deoxyuridine*G pair
?
-
nucleotide incison repair activity
-
-
?
duplex oligonucleotide containing a alpha-2'-deoxyadenosine*T pair
?
-
nucleotide incison repair activity
-
-
?
duplex oligonucleotide containing a tetrahydrofuran*G pair
?
-
nucleotide incison repair activity
-
-
?
oligodeoxynucleotide with abasic site 2,3-dihydroxy-5-oxopentyl phosphate
?
-
-
-
-
?
single-stranded DNA with abasic sites
?
-
catalytic efficiency is 20fold less than the activity against double-stranded DNA with abasic sites
-
-
?
DNA
fragments of DNA
base excision repair (BERa) pathway is initiated by lesion-specific glycosylases that excise the damaged base from the sugar-phosphate backbone, resulting in a potentially cytotoxic apurinic/apyrimidinic (AP) site intermediate that becomes the substrate for the major human AP endonuclease
-
-
?
DNA
fragments of DNA
-
-
648685, 648686, 648687, 694298, 701749, 702317, 702939, 703032, 703960, 704663, 704731, 704948, 705736, 706019, 706429
-
-
?
DNA
fragments of DNA
-
cleavage of apyrimidinic DNA both 5' and 3' to the site of damage in a ratio of 60:40, respectively, even though it can cleave on both sides of an internal apyrimidinic site, it does not release deoxyribose 5-phosphate from terminal apyrimidinic sites
-
?
DNA
fragments of DNA
-
acts on specific adenines in single-stranded DNA
-
?
DNA
fragments of DNA
-
cleaves single- and double-stranded oligonucleotides lacking one or two bases
-
?
DNA
fragments of DNA
enzyme reveals glycosylase activity and apurinic/apyrimidinic lyase activity on duplex DNA containing 8-OH-G, DNA containing 8-OH-G/A is not cleaved, DNA containing 8-OH-G/T and 8-OH-G/G is slightly cleaved
-
?
DNA
fragments of DNA
-
cleavage at abasic sites in duplexes with paired lesions is slower than in duplexes with single lesions. Double strand breaks are readily generated in duplexes with abasic sites positioned 3' to each other. In duplexes containing abasic sites set 1 base pair apart, 5' to each other, both enzymes slowly cleave the abasic site on one strand only and are unable to incise the other stand
-
?
DNA
fragments of DNA
-
acts on both 5-hydroxycytosine and abasic sites, preferentially when these are situated opposite guanines
-
?
DNA
fragments of DNA
-
catalyzes incision at the C4-keto-C-1-aldehyde site, hydrolyzes 3'-phosphoglycolates 25fold more slowly than C-4-keto-C-1-aldehydes
-
?
DNA
fragments of DNA
-
cleaves the DNA phosphodiester backbone immediately 5' to an AP site, also shows 3'-phosphodiesterase activity, 3'-phosphatase activity, RNaseH and significant 3'-5'-exonuclease activity
-
?
DNA
fragments of DNA
-
catalyzes 5'-incision of 2-deoxyribonolactone, but acts at least 10fold less effectively to remove the 3'-phosphates at direct strand breaks
-
?
DNA
fragments of DNA
cleaves thymine glycol-containing form I plasmid DNA and a dihydrouracil-containing oligonucleotide duplex
-
?
DNA
fragments of DNA
-
rate of AP lyase-mediated strand cleavage is much slower than the rate of DNA N-glycoxsylase-mediated base release
-
?
DNA
fragments of DNA
-
specific for DNA containing either apurinic or apyrimidinic sites
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?
DNA
fragments of DNA
-
endonuclease A: activity for UV-irradiated DNA, gamma-irradiated DNA and OsO4-treated DNA
-
?
DNA
fragments of DNA
-
bifunctional enzyme is involved in base excision repair, it is a bifunctional DNA glycosylase/apurinic/apyrimidinic lyase which removes hydrated, reduced, or oxidized bases from the DNA backbone as the initial step of base excision repair
-
-
?
DNA
fragments of DNA
-
DNA single-strand breaks containing 3'-blocking groups are generated from attack of the sugar backbone by reactive oxygen species or after base excision by DNA glycosylase/apurinic/apyrimidinic (AP) lyases
-
-
?
DNA
fragments of DNA
-
5'-deoxyribose-5-phosphate and apurinic/apyrimidinic sites are excised with half-lives of 2.7 and 7.0 min, respectively
-
-
?
DNA
fragments of DNA
-
Ape1 cleaves the phosphodiester backbone 5' to the AP site generating 3'-hydroxyl and 5'-deoxyribosephosphate termini, Ape1 exhibits a prominent 5' hydrolytic AP endonuclease, a weak 3'-diesterase and a 3'-5'-exonuclease activity
-
-
?
additional information
?
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enzyme lacks 3'-endonuclease activity against undamaged DNA
-
-
?
additional information
?
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enzyme lacks 3'-endonuclease activity against undamaged DNA
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?
additional information
?
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catalyses the initial step in apruinic/apyrimidinic site repair
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?
additional information
?
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catalyses the initial step in apruinic/apyrimidinic site repair
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?
additional information
?
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APE1 appears to have endonucleolytic activity as a repair enzyme within the nucleotide incision repair pathway
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?
additional information
?
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APE1 appears to have endonucleolytic activity as a repair enzyme within the nucleotide incision repair pathway
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?
additional information
?
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APE1 has been identified as a protein capable of nuclear redox activity, inducing the DNA binding activity of several transcription factors, such as activator protein-1, nuclear factor-kappaB, Myb, polyoma virus enhancer-binding protein-2, HLF, nuclear factor-Y, early growth response protein-1, hypoxia inducible factor-1alpha, ATF/CREB family, p53, and Pax proteins. In each case, this effect is accomplished by maintaining the cysteine residues of the transcription factors in the reduced state.
-
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?
additional information
?
-
APE1 hydrolytically cleaves the phosphodiester backbone 5' to the AP site, leaving a 3'-hydroxyl and a 5'-abasic deoxyribose phosphate to be processed by the subsequent cascade of BER enzymes
-
-
?
additional information
?
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APE1 hydrolytically cleaves the phosphodiester backbone 5' to the AP site, leaving a 3'-hydroxyl and a 5'-abasic deoxyribose phosphate to be processed by the subsequent cascade of BER enzymes
-
-
?
additional information
?
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APE1 is a fundamental protein in this essential repair pathway and is thought to be responsible for more than 95% of total AP endonuclease activity in human cell culture extracts
-
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?
additional information
?
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APE1 is a fundamental protein in this essential repair pathway and is thought to be responsible for more than 95% of total AP endonuclease activity in human cell culture extracts
-
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?
additional information
?
-
APE1 is directly responsible for the control of the intracellular ROS levels through its inhibitory effect on Rac1, the regulatory subunit of a membrane nonphagocytic NADPH oxidase system.
-
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?
additional information
?
-
APE1 recognizes AP sites in DNA that arise either spontaneously or as enzymatic products of DNA repair glycosylases that excise substrate base lesions as part of the base excision repair (BER) response. Subsequent to damage recognition, the chemistry central to the function of APE1 is wateractivated by a Mg2+ ion followed by hydrolytic cleavage of the phosphodiester bond immediately 5' to the abasic site
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?
additional information
?
-
APE1 utilizes a site located in its N-terminus for redox regulation of important transcription factors such as NF-kappaB, p53, c-Fos, and c-Jun
-
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?
additional information
?
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APE1 utilizes a site located in its N-terminus for redox regulation of important transcription factors such as NF-kappaB, p53, c-Fos, and c-Jun
-
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?
additional information
?
-
In addition to its primary AP site incision function, APE1 exhibits 3'-5' exonuclease, 3'-phosphodiesterase and RNase H catalysis, and a 3'-phosphatase activity
-
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?
additional information
?
-
-
In addition to its primary AP site incision function, APE1 exhibits 3'-5' exonuclease, 3'-phosphodiesterase and RNase H catalysis, and a 3'-phosphatase activity
-
-
?
additional information
?
-
multifunctional protein possessing both DNA repair and transcriptional regulatory activities, has a pleiotropic role in controlling cellular response to oxidative stress. APE1 is the main apurinic/apyrimidinic endonuclease in eukaryotic cells, playing a central role in the DNA base excision repair pathway of all DNA lesions (uracil, alkylated and oxidized, and abasic sites), including single-strand breaks, and has also co-transcriptional activity by modulating genes expression directly regulated by either ubiquitous and tissue specific transcription factors. It controls the intracellular redox state by inhibiting the reactive oxygen species production
-
-
?
additional information
?
-
25-mer oligonucleotide 5'-labeled with P32 containing tetrahydrofuran as abasic site analog
-
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?
additional information
?
-
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25-mer oligonucleotide 5'-labeled with P32 containing tetrahydrofuran as abasic site analog
-
-
?
additional information
?
-
APE1 promotes the removal of a TNR hairpin during BER of a base lesion in the hairpin loop region. This is accomplished by the 3'-5'-exonuclease activity of the enzyme that cleaved the upstream 3'-region exonucleolytically, resolving the double-flap intermediate and preventing TNR expansions. APE1 significantly stimulates the ligation activity of LIG I to specifically facilitate the completion of hairpin removal. This is the first evidence of APE1 preventing TNR expansions by facilitating hairpin removal
-
-
?
additional information
?
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-
APE1 promotes the removal of a TNR hairpin during BER of a base lesion in the hairpin loop region. This is accomplished by the 3'-5'-exonuclease activity of the enzyme that cleaved the upstream 3'-region exonucleolytically, resolving the double-flap intermediate and preventing TNR expansions. APE1 significantly stimulates the ligation activity of LIG I to specifically facilitate the completion of hairpin removal. This is the first evidence of APE1 preventing TNR expansions by facilitating hairpin removal
-
-
?
additional information
?
-
in vivo, APE1 is acetylated (AcAPE1) after binding to the AP sites in chromatin and that AcAPE1 is exclusively present on chromatin throughout the cell cycle. Positive charges of acetylable lysine residues in the N-terminal domain of APE1 are essential for chromatin association. Acetylation-mediated neutralization of the positive charges of the lysine residues in the N-terminal domain of APE1 induces a conformational change; this in turn enhances the AP endonuclease activity of APE1. In the absence of APE1 acetylation, cells accumulate AP sites in the genome and show higher sensitivity to DNA-damaging agents. Positive charges of acetylable Lys residues but not their acetylation are essential for the chromatin binding of APE1
-
-
?
additional information
?
-
-
in vivo, APE1 is acetylated (AcAPE1) after binding to the AP sites in chromatin and that AcAPE1 is exclusively present on chromatin throughout the cell cycle. Positive charges of acetylable lysine residues in the N-terminal domain of APE1 are essential for chromatin association. Acetylation-mediated neutralization of the positive charges of the lysine residues in the N-terminal domain of APE1 induces a conformational change; this in turn enhances the AP endonuclease activity of APE1. In the absence of APE1 acetylation, cells accumulate AP sites in the genome and show higher sensitivity to DNA-damaging agents. Positive charges of acetylable Lys residues but not their acetylation are essential for the chromatin binding of APE1
-
-
?
additional information
?
-
The enzyme cleaves an AP site in DNA via Mg2+-dependent hydrolytic mechanism producing a 5'-deoxyribose phosphate and 3'-hydroxyl and, therefore, the interaction with AP sites via the Schiff base formation, which is characteristic of the beta-elimination mechanism, is not required for APE1 catalytic activity
-
-
?
additional information
?
-
-
The enzyme cleaves an AP site in DNA via Mg2+-dependent hydrolytic mechanism producing a 5'-deoxyribose phosphate and 3'-hydroxyl and, therefore, the interaction with AP sites via the Schiff base formation, which is characteristic of the beta-elimination mechanism, is not required for APE1 catalytic activity
-
-
?
additional information
?
-
the mechanism of catalysis of the APE1 endonuclease reaction includes nucleophilic attack by a hydroxide ion on the phosphorous atom at the 5'-side from AP site. The hydroxide ion is formed from a water molecule activated by the Asp210 residue. The transition complex is stabilized via formation of hydrogen bonds with the Asn174, Asn212, and His309/Asp283 residues. Glu96 participates in binding of one Mg2+, which coordinates the leaving O3'-group, and Asp210 and His309 coordinate a second metal ion participating in formation of a hydroxide ion from a water molecule. A transition state with the phosphorous atom is formed because of the nucleophilic attack, the destabilized P-O3' bond is cleaved, and, as a result, inversion of the phosphate configuration occurs (SN2-mechanism). Slow dissociation of the APE1-DNA complex (product) prevents accumulation of single-strand breaks in DNA. The reaction rate of this step increases with increase in Mg2+ concentration and, as a result, the catalysis itself likely becomes the limiting step. Mechanism of the P-O3' bond cleavage at the 5'-side of an AP site catalyzed by human APE1 derived from the structure of the APE1-DNA complex produced by X-ray at higher resolution, overview
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-
?
additional information
?
-
-
the mechanism of catalysis of the APE1 endonuclease reaction includes nucleophilic attack by a hydroxide ion on the phosphorous atom at the 5'-side from AP site. The hydroxide ion is formed from a water molecule activated by the Asp210 residue. The transition complex is stabilized via formation of hydrogen bonds with the Asn174, Asn212, and His309/Asp283 residues. Glu96 participates in binding of one Mg2+, which coordinates the leaving O3'-group, and Asp210 and His309 coordinate a second metal ion participating in formation of a hydroxide ion from a water molecule. A transition state with the phosphorous atom is formed because of the nucleophilic attack, the destabilized P-O3' bond is cleaved, and, as a result, inversion of the phosphate configuration occurs (SN2-mechanism). Slow dissociation of the APE1-DNA complex (product) prevents accumulation of single-strand breaks in DNA. The reaction rate of this step increases with increase in Mg2+ concentration and, as a result, the catalysis itself likely becomes the limiting step. Mechanism of the P-O3' bond cleavage at the 5'-side of an AP site catalyzed by human APE1 derived from the structure of the APE1-DNA complex produced by X-ray at higher resolution, overview
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-
?
additional information
?
-
a fluorophore-labelled 17-mer oligonucleotide DNA substrate is used
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-
?
additional information
?
-
-
a fluorophore-labelled 17-mer oligonucleotide DNA substrate is used
-
-
?
additional information
?
-
analysis of enzyme activity and kinetics with DNA substrates comprising duplexes of deoxyribonucleotides with one 5'-dangling end that contain a fluorescent 2-aminopurine residue at the 1st, 2nd, 4th, or 6th position from the 3'-end of the short oligonucleotide. The impact of the 3'-end nucleotide, which contains mismatched, undamaged bases or modified bases as well as an abasic site or phosphate group, on the efficiency of 3'-5'-exonuclease activity is determined. The rate-limiting step of 3'-nucleotide removal by APE1 in the 3'-5'-exonuclease process is the release of the detached nucleotide from the enzyme's active site. Exonuclease activity of APE1 is effective toward duplexes containing gaps or 5'-dangling ends. For the kinetic analysis of the 3'-5'-exonuclease reaction, the duplexes of 15 and 28 nucleotides (nt) with a 5'-dangling end served as model DNA substrates
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-
?
additional information
?
-
-
analysis of enzyme activity and kinetics with DNA substrates comprising duplexes of deoxyribonucleotides with one 5'-dangling end that contain a fluorescent 2-aminopurine residue at the 1st, 2nd, 4th, or 6th position from the 3'-end of the short oligonucleotide. The impact of the 3'-end nucleotide, which contains mismatched, undamaged bases or modified bases as well as an abasic site or phosphate group, on the efficiency of 3'-5'-exonuclease activity is determined. The rate-limiting step of 3'-nucleotide removal by APE1 in the 3'-5'-exonuclease process is the release of the detached nucleotide from the enzyme's active site. Exonuclease activity of APE1 is effective toward duplexes containing gaps or 5'-dangling ends. For the kinetic analysis of the 3'-5'-exonuclease reaction, the duplexes of 15 and 28 nucleotides (nt) with a 5'-dangling end served as model DNA substrates
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-
?
additional information
?
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APE1 cleaved AP sites in the structure of DNA/RNAx02hybrid (DNA strand), singlex02stranded RNA, single-stranded DNA, and double-stranded regions of pseudo-triplex DNA-RNA complexes modeling replication and transcription intermediates. APE1 exhibits endonuclease activity during hydrolysis of an AP site on a single-stranded DNA. The activity on the single-stranded DNA is 20fold lower than on double-stranded DNA. As in the case of double-stranded DNA, endonuclease activity of APE1 depended on the presence of magnesium ions. the cleavage of single-stranded DNA with an AP site does not depend on the presence of DNA glycosylases, and it is not inhibited by the reaction product. Complexes of APE1 with double-stranded DNA containing an tetrahydrofuran residue in the center of a non-cleaved strand are not detected
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additional information
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APE1 cleaved AP sites in the structure of DNA/RNAx02hybrid (DNA strand), singlex02stranded RNA, single-stranded DNA, and double-stranded regions of pseudo-triplex DNA-RNA complexes modeling replication and transcription intermediates. APE1 exhibits endonuclease activity during hydrolysis of an AP site on a single-stranded DNA. The activity on the single-stranded DNA is 20fold lower than on double-stranded DNA. As in the case of double-stranded DNA, endonuclease activity of APE1 depended on the presence of magnesium ions. the cleavage of single-stranded DNA with an AP site does not depend on the presence of DNA glycosylases, and it is not inhibited by the reaction product. Complexes of APE1 with double-stranded DNA containing an tetrahydrofuran residue in the center of a non-cleaved strand are not detected
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additional information
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APE1 the base excision DNA repair system catalyzes the hydrolysis of the phosphodiester bond on the 5'-side of an apurinic/apyrimidinic site (AP-site) to give the 5'-phosphate and 3'-hydroxyl group. APE1 exhibits also 3'-5'-exonuclease activity albeit less pronounced compared to its endonuclease activity
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additional information
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APE1 the base excision DNA repair system catalyzes the hydrolysis of the phosphodiester bond on the 5'-side of an apurinic/apyrimidinic site (AP-site) to give the 5'-phosphate and 3'-hydroxyl group. APE1 exhibits also 3'-5'-exonuclease activity albeit less pronounced compared to its endonuclease activity
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additional information
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diverse BS-AP DNA duplexes as substrates. Purified recombinant human APE1 is capable of forming the 50 kDa-adducts with efficiency of BS-AP DNAs cross-linking to APE1 being dependent on the mutual orientation of AP sites. Identification of APE1 as a target of cross-linking to BS-AP DNA, and cross-linking of cell extract proteins from HeLa cell cell extract to AP DNA with bistranded AP sites, and AP endonuclease activity of APE1 on BS-AP DNAs, detailed overview
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additional information
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diverse BS-AP DNA duplexes as substrates. Purified recombinant human APE1 is capable of forming the 50 kDa-adducts with efficiency of BS-AP DNAs cross-linking to APE1 being dependent on the mutual orientation of AP sites. Identification of APE1 as a target of cross-linking to BS-AP DNA, and cross-linking of cell extract proteins from HeLa cell cell extract to AP DNA with bistranded AP sites, and AP endonuclease activity of APE1 on BS-AP DNAs, detailed overview
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additional information
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electron microscopy imaging of APE1-DNA complexes reveals oligomerization of APE1 along the DNA duplex and APE1-mediated DNA bridging followed by DNA aggregation. APE1 polymerizes on both undamaged and damaged DNA in cooperative mode. Duplex DNA and diverse oligonucleotides with single base lesion are used as substrates, stopped-flow fluorescence measurements
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additional information
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electron microscopy imaging of APE1-DNA complexes reveals oligomerization of APE1 along the DNA duplex and APE1-mediated DNA bridging followed by DNA aggregation. APE1 polymerizes on both undamaged and damaged DNA in cooperative mode. Duplex DNA and diverse oligonucleotides with single base lesion are used as substrates, stopped-flow fluorescence measurements
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additional information
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fluorescent-labeled oligodeoxynucleotides substrates are used, overview
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additional information
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fluorescent-labeled oligodeoxynucleotides substrates are used, overview
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additional information
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human apurinic/apyrimidinic (AP) endonuclease APE1 catalyses the hydrolysis of phosphodiester bonds on the 5'-side of an AP-site (in the base excision repair pathway) and of some damaged nucleotides (in the nucleotide incision repair pathway). The range of substrate specificity includes structurally unrelated damaged nucleotides. Analysis of the mechanism of broad substrate specificity of APE1, overview. Substrate specificity and substrate binding, molecular dynamics simulations. The damaged nucleotide is everted from the DNA helix and placed into the enzyme's binding pocket, which is formed by Asn174, Asn212, Asn229, Ala230, Phe266, and Trp280. Nevertheless, no damage-specific contacts are detected between these amino acid residues in the active site of the enzyme and model damaged substrates containing 1,N6-ethenoadenosine, alpha-adenosine, 5,6-dihydrouridine, or F-site. The substrate specificity of APE1 is controlled by the ability of a damaged nucleotide to flip out from the DNA duplex in response to an enzyme-induced DNA distortion
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additional information
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human apurinic/apyrimidinic (AP) endonuclease APE1 catalyses the hydrolysis of phosphodiester bonds on the 5'-side of an AP-site (in the base excision repair pathway) and of some damaged nucleotides (in the nucleotide incision repair pathway). The range of substrate specificity includes structurally unrelated damaged nucleotides. Analysis of the mechanism of broad substrate specificity of APE1, overview. Substrate specificity and substrate binding, molecular dynamics simulations. The damaged nucleotide is everted from the DNA helix and placed into the enzyme's binding pocket, which is formed by Asn174, Asn212, Asn229, Ala230, Phe266, and Trp280. Nevertheless, no damage-specific contacts are detected between these amino acid residues in the active site of the enzyme and model damaged substrates containing 1,N6-ethenoadenosine, alpha-adenosine, 5,6-dihydrouridine, or F-site. The substrate specificity of APE1 is controlled by the ability of a damaged nucleotide to flip out from the DNA duplex in response to an enzyme-induced DNA distortion
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additional information
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substrates are DNA oligonucleotides which contain an 8-oxoguanine (8-oxoG). APE1 fails to directly stimulate FEN1 cleavage on a double-flap intermediate. APE1 promotes the production of the unexpanded repair product by stimulating LIG I
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additional information
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substrates are DNA oligonucleotides which contain an 8-oxoguanine (8-oxoG). APE1 fails to directly stimulate FEN1 cleavage on a double-flap intermediate. APE1 promotes the production of the unexpanded repair product by stimulating LIG I
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additional information
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usage of a fluorescence-based APE1 endonuclease activity assay and a plasmid DNA nicking assay
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additional information
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usage of a fluorescence-based APE1 endonuclease activity assay and a plasmid DNA nicking assay
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additional information
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gelonin, pokeweed antiviral protein and ricin belong to the family of ribosome-inactivating proteins with DNA-glycosylase/AP-lyase activities
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additional information
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unlike other endonucleases endonuclease IV or Exo III, Ape1 does not enhance the rate of product release with a G/A substrate
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additional information
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enzyme also has DNA N-glycosylase activity
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additional information
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enzyme has no biologically significant 3'-5'-exonuclease activity, the activity only manifests at enzyme concentrations elevated by 6-7 orders magnitude, activity does not show a preference to mismatched compared to matched DNA structures as well as to nicked or gapped DNA substrates
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additional information
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enzyme stimulates polymerase beta activity on the 5'-terminal oxidized abasic residue
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additional information
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corrects apurinic/apyrimidinic sites in the genome
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additional information
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multifunctional enzyme involved in DNA repair and redox regulation of transcription factors
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additional information
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key enzyme in repair of oxidatively damaged DNA
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additional information
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enzyme stimulates long patch base excision repair by cleaving the DNA and then facilitating the sequential binding and catalysis by DNA polymerase beta, DNA polymerase delta, FEN1 and DNA ligase I
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additional information
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AP endonuclease Ape1 is involved in the nucleotide incision repair pathway
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additional information
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APE1 exonuclease function appears to be modulated by the other BER proteins DNA polymerase beta and poly(ADP-ribose) polymerase 1. Excess APE1 over DNA polymerase beta may allow APE1 to perform both exonuclease function and stimulation of strand-displacement DNA synthesis by DNA polymerase beta
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additional information
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the enzyme enhances methylpurine-DNA glycosylase-catalyzed excision, complex formation of methylpurine-DNA glycosylase eith proliferating cell nuclear antigen can accomodate binding of APE1
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additional information
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the function of APE is considered as the rate-limiting step in DNA base excision repair. AP endonuclease suppresses DNA mismatch repair activity leading to microsatellite instability
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additional information
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hOgg1 protein catalyzes the excision of 8-oxo-7,8-dihydroguanine and the incision of apurinic and apyrimidinic sites in DNA
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additional information
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hOgg1 protein catalyzes the excision of 8-oxo-7,8-dihydroguanine and the incision of apurinic and apyrimidinic sites in DNA
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additional information
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the enzyme remains bound to its incision product when the 5'-incision us in double-stranded DNA. The enzyme dissociates from its single-stranded 5'-incised product
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additional information
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a DNA base excision repair enzyme with a wide variety of functions, including AP endonuclease (cleaving an AP site 5' to a deoxyribose phosphate moiety), 3' exonuclease, 3' phosphodiesterase, 3' phosphatase, RNaseH, and 5' endonuclease activities
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additional information
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AP endo acts by a one-step associative phosphoryl transfer mechanism on a THF-containing substrate
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additional information
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AP endo acts on many types of DNA substrate molecules but demonstrates the most robust activity when acting as a class II AP endonuclease
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additional information
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APE/Ref-1 is a critical component of the hypoxia-inducible transcriptional complex that interacts with hypoxia-inducible factor-1 and p300
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additional information
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APE/Ref-1 is a key regulator, it markedly induces and efficiently protects melanocytes from oxidative damage by inducing the antiapoptotic machinery and stimulating cell survival
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additional information
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APE1 can incise DNA at the 5'-position of oxidized pyrimidine bases such as 5,6-dihydro-thymine or 5,6-dihydro-2'-deoxyuracil (DHU), thus initiating a repair process known as nucleotide incision repair (NIR)
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additional information
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APE1 has DNA 3'-phosphatase activity in vitro and 3' to 5' exonuclease activity, which could be physiologically relevant in the removal of mismatched or damaged nucleotides incorporated during the synthesis step of BER
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additional information
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Ape1 has the ability to incise at AP sites in DNA conformations formed during DNA replication, transcription, and class switch recombination, and that Ape1 can endonucleolytically destroy damaged RNA
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additional information
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Ape1 is a multifunctional enzyme of 318 amino acids with redox-dependent regulation of transcription factors, 3' to 5' exonuclease, 3' phosphodiesterase, RNaseH and class II type AP endonuclease activities
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additional information
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APE1 is also named as redox effector factor-1 because of its redox abilities on different redox-regulated transcription factors
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additional information
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APE1/Ref-1 also has a complex relationship to high-mobility group box 1, a protein secreted by immune cells in response to inflammatory stimuli. APE1/Ref-1 can both promote and suppress inflammatory signaling induced by high-mobility group box 1
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additional information
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APE1/Ref-1 plays a complex role in the activation of nuclear factor kappa B, a key transcription factor involved in inflammatory and immune signaling
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additional information
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APE1/Ref-1 plays a role in cardiovascular physiology and pathophysiology. APE1/Ref-1 suppresses myocardial ischemia-reperfusion injury and vascular inflammation, and promotes endothelium-dependent vascular relaxation
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additional information
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APE1/Ref-1 promotes the effect of angiotensin II on Ca2+-activated K+-channel in human endothelial cells via suppression of NADPH oxidase
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additional information
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APE1/Ref-1 reduces oxidative stress by regulating the level of reactive oxygen species in the cytoplasm
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additional information
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APEs have 2 intrinsic activities in DNA repair. They act as an endonuclease in cleaving AP sites to generate 3' OH and 5' phosphodeoxyribose termini. They also act as a 3' phosphodiesterase/exonuclease to remove 3' blocking phosphodeoxyribose or its fragments generated during strand breaks, and by reactive oxygen species or DNA glycosylases that excise oxidized bases in the first step of base excision repair
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additional information
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enzyme cleaves the AP sites in DNA and allows them to be repaired by other enzymes involved in base excision repair
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additional information
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enzyme has an essential base excision repair (BER) activity and a redox activity that regulates expression of a number of genes through reduction of their transcription factors, AP-1, NFkappaB, HIF-1alpha, CREB, p53 and others
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additional information
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enzyme has the ability to reductively activate redoxsensitive transcription factors and negative gene regulation by extracellular calcium
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additional information
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enzyme stimulates the DNA binding activity of the AP-1 family of transcription factors via a redox-dependent mechanism
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additional information
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forced cytoplasmic overexpression of APE1 profoundly attenuates the upregulation of high-mobility group box 1-mediated reactive oxygen species generation, cytokine secretion, and cyclooxygenase-2 expression by primary monocytes and macrophage-like THP-1 cell lines
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additional information
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high-mobility group box 1-induced activation of p38 and c-Jun N-terminal kinase is strongly abrogated by the overexpression of APE1
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additional information
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hNTH1 and Y-box-binding protein-1 may be part of the same DNA repair pathway in response to cisplatin and UV treatments
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additional information
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hNTH1 binds directly to Y-box-binding protein-1 in the absence of nucleic acids, it binds to the auto-inhibitory n-terminal tail of NTH1
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additional information
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human Ape1 is a multifunctional protein with a major role in initiating repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage
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additional information
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human apurinic/apyrimidinic endonuclease 1 is a major constituent of the base excision repair (BER) pathway of AP sites of DNA lesions. APE1 specifically binds to abasic sites and cuts the 5'-phosphodiester bond with its endonuclease activity to produce a DNA primer with 3'-hydroxyl end, which is a required step in the BER repair pathway
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additional information
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human endonuclease III is a relevant target to potentiate cisplatin cytotoxicity in Y-box-binding protein-1 overexpressing tumor cells
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additional information
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In addition to the exonuclease function, human APE1 is endowed with another enzymatic activity potentially relevant for the protection against oxidative damage
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additional information
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In human cells, APE1 excises sugar fragments that block the 3'-ends thus facilitating DNA repair synthesis
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additional information
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major factor in the maintenance of the integrity of the human genome
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additional information
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multifunctional protein involved in base excision DNA repair and in transcriptional regulation of gene expression, importance to genomic stability and cell survival
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additional information
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multifunctional protein involved in reduction-oxidation regulation. It functions as a redox factor that maintains transcription factors in an active reduced state
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additional information
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overexpression of APE1/Ref-1 suppressed angiotensin II induced production of superoxide and hydrogen peroxide
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additional information
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small interfering RNA knockdown of endogenous APE1 impairs high-mobility group box 1-mediated cytokine expression and MAPK activation in THP-1 cells. High-mobility group box 1-stimulation induces the translocation of APE1 to the nucleus of the cell
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additional information
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The BK-Ca current in APE1/Ref-1-overexpressing human umbilical vein endothelial cells is similarly inhibited by angiotensin II, except that inhibition of 43.06% is achieved using only 10 nM angiotensin II
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additional information
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the DNA-binding ability of NF-kappaB in the Ape1/Ref-1 expressing cells is significantly increased
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additional information
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the key function is to produce a 3' OH terminus that serves as a primer for repair synthesis.
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additional information
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ubiquitously expressed protein that functions as both an endonuclease in the repair of oxidatively damaged DNA and an aid in the binding of redox-sensitive transcription factors
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additional information
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AP endo cleaves the Rp but not the Sp stereoisomer of DNA phosphorothioate oligomers, albeit slowly with respect to a phosphodiester substrate
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additional information
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The ratio of AP endo reaction product to STM7 49mer hairpin oligomers is varied. Product formation is maximal with an 8:1 ratio of STM7 acceptor to 5' thiophosphate donor DNA and by addition of extra ATP (0.5 mM) and ligase (60 units) midreaction
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additional information
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Used oligonucleotides are 54mers annealed to a complementary 18mer DNA to form the partial duplex substrates (54F-endbubble or 54F-centerbubble with 18DNA) and two 54mers annealed to create an 18-nt bubble structure (54Fendbubble or 54Fcenterbubble with 54bubble18comp). The abasic site is either centrally located (center bubble DNAs) or located at the ssDNA-dsDNA junction (end bubble DNAs). Ape1 most efficiently incised at an abasic site located centrally in the 18-nt bubble structure (54Fcenterbubble18-54bubblecomp), followed by the centrally located abasic site in the partial duplex DNA (54Fcenterbubble18-18DNA), the abasic site at an ssDNA/dsDNA junction in the bubble conformation (54Fendbubble18-54bubblecomp), and the abasic site at an ssDNA/dsDNA junction in partial duplex DNA (54Fendbubble18-18DNA)
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additional information
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APE1 at low concentrations does not have any effect on 5'-Cy3-CrUAGGTAGTTATCCrUAG-Black Hole Quencher1-3' (OligoII), under similar conditions, the recombinant APE1 has no effect on fluorescently labeled or 32P-labeled DNAOligoI
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additional information
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a 2'-OH on the sugar moiety is absolutely required for RNA cleavage by wild-type APE1, consistent with APE1 leaving a 3'-PO4 2? group following cleavage of RNA. the catalytic mechanisms for cleaving RNA, abasic single-stranded RNA, and abasic DNA are not identical
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additional information
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APE1 adopts a partially unfolded state, which is proposed to be the redox active form of the enzyme
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additional information
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DNA polymerase beta approaches the Ape1-DNA complex downstream of the incision site, displaces Ape1-DNA binding contacts including residues K227, K228, and K276, and in the process makes minimal interactions with lysine residues in the Ref1 domain, i.e. N-terminal residues 43-93
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additional information
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wild-type APE1 undergoes at least four conformational transitions during the processing of abasic sites in DNA. Nonspecific interactions of APE1 with undamaged DNA can be described by a two-step kinetic scheme. APE1 molecule undergoes at least four conformational transitions, including nonspecific encounter complex formation, mutual adjustment of the enzyme and DNA substrate structures for catalysis, catalytic incision of the substrate, and release of the enzyme from its complex with the product. The C1'-hydroxyl moiety of the abasic site is required for the most effective recognition and catalysis
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
AP-DNA
fragments of DNA
Base excision repair pathway, enzyme cleaves the 5'-phosphodiester bond, generating 3'-OH and 5'-dRP termini
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DNA containing apurinic/apyrimidinic sites
fragments of DNA
hydrogen bonds to phosphate groups 3' to the cleavage site is essential for the binding of the enzyme to the product DNA, which may be necessary for efficient functioning of the base excision rapair pathway
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DNA containing tamdem dihydrouracil
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the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
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DNA containing tandem dihydrouracil
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the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
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DNA
fragments of DNA
base excision repair (BERa) pathway is initiated by lesion-specific glycosylases that excise the damaged base from the sugar-phosphate backbone, resulting in a potentially cytotoxic apurinic/apyrimidinic (AP) site intermediate that becomes the substrate for the major human AP endonuclease
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DNA
fragments of DNA
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648636, 648638, 648657, 648661, 648663, 648664, 648666, 648667, 648672, 648673, 648674, 648676, 648677, 648678, 648682, 648685, 648686, 648687, 694298, 702939, 704731
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DNA
fragments of DNA
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bifunctional enzyme is involved in base excision repair, it is a bifunctional DNA glycosylase/apurinic/apyrimidinic lyase which removes hydrated, reduced, or oxidized bases from the DNA backbone as the initial step of base excision repair
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DNA
fragments of DNA
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DNA single-strand breaks containing 3'-blocking groups are generated from attack of the sugar backbone by reactive oxygen species or after base excision by DNA glycosylase/apurinic/apyrimidinic (AP) lyases
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additional information
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catalyses the initial step in apruinic/apyrimidinic site repair
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additional information
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catalyses the initial step in apruinic/apyrimidinic site repair
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additional information
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APE1 appears to have endonucleolytic activity as a repair enzyme within the nucleotide incision repair pathway
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additional information
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APE1 appears to have endonucleolytic activity as a repair enzyme within the nucleotide incision repair pathway
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additional information
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APE1 has been identified as a protein capable of nuclear redox activity, inducing the DNA binding activity of several transcription factors, such as activator protein-1, nuclear factor-kappaB, Myb, polyoma virus enhancer-binding protein-2, HLF, nuclear factor-Y, early growth response protein-1, hypoxia inducible factor-1alpha, ATF/CREB family, p53, and Pax proteins. In each case, this effect is accomplished by maintaining the cysteine residues of the transcription factors in the reduced state.
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additional information
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APE1 hydrolytically cleaves the phosphodiester backbone 5' to the AP site, leaving a 3'-hydroxyl and a 5'-abasic deoxyribose phosphate to be processed by the subsequent cascade of BER enzymes
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additional information
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APE1 hydrolytically cleaves the phosphodiester backbone 5' to the AP site, leaving a 3'-hydroxyl and a 5'-abasic deoxyribose phosphate to be processed by the subsequent cascade of BER enzymes
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additional information
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APE1 is a fundamental protein in this essential repair pathway and is thought to be responsible for more than 95% of total AP endonuclease activity in human cell culture extracts
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additional information
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APE1 is a fundamental protein in this essential repair pathway and is thought to be responsible for more than 95% of total AP endonuclease activity in human cell culture extracts
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additional information
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APE1 is directly responsible for the control of the intracellular ROS levels through its inhibitory effect on Rac1, the regulatory subunit of a membrane nonphagocytic NADPH oxidase system.
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additional information
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APE1 recognizes AP sites in DNA that arise either spontaneously or as enzymatic products of DNA repair glycosylases that excise substrate base lesions as part of the base excision repair (BER) response. Subsequent to damage recognition, the chemistry central to the function of APE1 is wateractivated by a Mg2+ ion followed by hydrolytic cleavage of the phosphodiester bond immediately 5' to the abasic site
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additional information
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APE1 utilizes a site located in its N-terminus for redox regulation of important transcription factors such as NF-kappaB, p53, c-Fos, and c-Jun
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additional information
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APE1 utilizes a site located in its N-terminus for redox regulation of important transcription factors such as NF-kappaB, p53, c-Fos, and c-Jun
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additional information
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In addition to its primary AP site incision function, APE1 exhibits 3'-5' exonuclease, 3'-phosphodiesterase and RNase H catalysis, and a 3'-phosphatase activity
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additional information
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In addition to its primary AP site incision function, APE1 exhibits 3'-5' exonuclease, 3'-phosphodiesterase and RNase H catalysis, and a 3'-phosphatase activity
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additional information
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multifunctional protein possessing both DNA repair and transcriptional regulatory activities, has a pleiotropic role in controlling cellular response to oxidative stress. APE1 is the main apurinic/apyrimidinic endonuclease in eukaryotic cells, playing a central role in the DNA base excision repair pathway of all DNA lesions (uracil, alkylated and oxidized, and abasic sites), including single-strand breaks, and has also co-transcriptional activity by modulating genes expression directly regulated by either ubiquitous and tissue specific transcription factors. It controls the intracellular redox state by inhibiting the reactive oxygen species production
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additional information
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APE1 promotes the removal of a TNR hairpin during BER of a base lesion in the hairpin loop region. This is accomplished by the 3'-5'-exonuclease activity of the enzyme that cleaved the upstream 3'-region exonucleolytically, resolving the double-flap intermediate and preventing TNR expansions. APE1 significantly stimulates the ligation activity of LIG I to specifically facilitate the completion of hairpin removal. This is the first evidence of APE1 preventing TNR expansions by facilitating hairpin removal
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additional information
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APE1 promotes the removal of a TNR hairpin during BER of a base lesion in the hairpin loop region. This is accomplished by the 3'-5'-exonuclease activity of the enzyme that cleaved the upstream 3'-region exonucleolytically, resolving the double-flap intermediate and preventing TNR expansions. APE1 significantly stimulates the ligation activity of LIG I to specifically facilitate the completion of hairpin removal. This is the first evidence of APE1 preventing TNR expansions by facilitating hairpin removal
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additional information
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in vivo, APE1 is acetylated (AcAPE1) after binding to the AP sites in chromatin and that AcAPE1 is exclusively present on chromatin throughout the cell cycle. Positive charges of acetylable lysine residues in the N-terminal domain of APE1 are essential for chromatin association. Acetylation-mediated neutralization of the positive charges of the lysine residues in the N-terminal domain of APE1 induces a conformational change; this in turn enhances the AP endonuclease activity of APE1. In the absence of APE1 acetylation, cells accumulate AP sites in the genome and show higher sensitivity to DNA-damaging agents. Positive charges of acetylable Lys residues but not their acetylation are essential for the chromatin binding of APE1
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additional information
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in vivo, APE1 is acetylated (AcAPE1) after binding to the AP sites in chromatin and that AcAPE1 is exclusively present on chromatin throughout the cell cycle. Positive charges of acetylable lysine residues in the N-terminal domain of APE1 are essential for chromatin association. Acetylation-mediated neutralization of the positive charges of the lysine residues in the N-terminal domain of APE1 induces a conformational change; this in turn enhances the AP endonuclease activity of APE1. In the absence of APE1 acetylation, cells accumulate AP sites in the genome and show higher sensitivity to DNA-damaging agents. Positive charges of acetylable Lys residues but not their acetylation are essential for the chromatin binding of APE1
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additional information
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The enzyme cleaves an AP site in DNA via Mg2+-dependent hydrolytic mechanism producing a 5'-deoxyribose phosphate and 3'-hydroxyl and, therefore, the interaction with AP sites via the Schiff base formation, which is characteristic of the beta-elimination mechanism, is not required for APE1 catalytic activity
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additional information
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The enzyme cleaves an AP site in DNA via Mg2+-dependent hydrolytic mechanism producing a 5'-deoxyribose phosphate and 3'-hydroxyl and, therefore, the interaction with AP sites via the Schiff base formation, which is characteristic of the beta-elimination mechanism, is not required for APE1 catalytic activity
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additional information
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the mechanism of catalysis of the APE1 endonuclease reaction includes nucleophilic attack by a hydroxide ion on the phosphorous atom at the 5'-side from AP site. The hydroxide ion is formed from a water molecule activated by the Asp210 residue. The transition complex is stabilized via formation of hydrogen bonds with the Asn174, Asn212, and His309/Asp283 residues. Glu96 participates in binding of one Mg2+, which coordinates the leaving O3'-group, and Asp210 and His309 coordinate a second metal ion participating in formation of a hydroxide ion from a water molecule. A transition state with the phosphorous atom is formed because of the nucleophilic attack, the destabilized P-O3' bond is cleaved, and, as a result, inversion of the phosphate configuration occurs (SN2-mechanism). Slow dissociation of the APE1-DNA complex (product) prevents accumulation of single-strand breaks in DNA. The reaction rate of this step increases with increase in Mg2+ concentration and, as a result, the catalysis itself likely becomes the limiting step. Mechanism of the P-O3' bond cleavage at the 5'-side of an AP site catalyzed by human APE1 derived from the structure of the APE1-DNA complex produced by X-ray at higher resolution, overview
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additional information
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the mechanism of catalysis of the APE1 endonuclease reaction includes nucleophilic attack by a hydroxide ion on the phosphorous atom at the 5'-side from AP site. The hydroxide ion is formed from a water molecule activated by the Asp210 residue. The transition complex is stabilized via formation of hydrogen bonds with the Asn174, Asn212, and His309/Asp283 residues. Glu96 participates in binding of one Mg2+, which coordinates the leaving O3'-group, and Asp210 and His309 coordinate a second metal ion participating in formation of a hydroxide ion from a water molecule. A transition state with the phosphorous atom is formed because of the nucleophilic attack, the destabilized P-O3' bond is cleaved, and, as a result, inversion of the phosphate configuration occurs (SN2-mechanism). Slow dissociation of the APE1-DNA complex (product) prevents accumulation of single-strand breaks in DNA. The reaction rate of this step increases with increase in Mg2+ concentration and, as a result, the catalysis itself likely becomes the limiting step. Mechanism of the P-O3' bond cleavage at the 5'-side of an AP site catalyzed by human APE1 derived from the structure of the APE1-DNA complex produced by X-ray at higher resolution, overview
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additional information
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enzyme stimulates polymerase beta activity on the 5'-terminal oxidized abasic residue
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additional information
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corrects apurinic/apyrimidinic sites in the genome
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additional information
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multifunctional enzyme involved in DNA repair and redox regulation of transcription factors
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additional information
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key enzyme in repair of oxidatively damaged DNA
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additional information
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enzyme stimulates long patch base excision repair by cleaving the DNA and then facilitating the sequential binding and catalysis by DNA polymerase beta, DNA polymerase delta, FEN1 and DNA ligase I
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additional information
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AP endonuclease Ape1 is involved in the nucleotide incision repair pathway
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additional information
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APE1 exonuclease function appears to be modulated by the other BER proteins DNA polymerase beta and poly(ADP-ribose) polymerase 1. Excess APE1 over DNA polymerase beta may allow APE1 to perform both exonuclease function and stimulation of strand-displacement DNA synthesis by DNA polymerase beta
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additional information
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the enzyme enhances methylpurine-DNA glycosylase-catalyzed excision, complex formation of methylpurine-DNA glycosylase eith proliferating cell nuclear antigen can accomodate binding of APE1
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additional information
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the function of APE is considered as the rate-limiting step in DNA base excision repair. AP endonuclease suppresses DNA mismatch repair activity leading to microsatellite instability
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additional information
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a DNA base excision repair enzyme with a wide variety of functions, including AP endonuclease (cleaving an AP site 5' to a deoxyribose phosphate moiety), 3' exonuclease, 3' phosphodiesterase, 3' phosphatase, RNaseH, and 5' endonuclease activities
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additional information
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AP endo acts by a one-step associative phosphoryl transfer mechanism on a THF-containing substrate
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additional information
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AP endo acts on many types of DNA substrate molecules but demonstrates the most robust activity when acting as a class II AP endonuclease
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additional information
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APE/Ref-1 is a critical component of the hypoxia-inducible transcriptional complex that interacts with hypoxia-inducible factor-1 and p300
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additional information
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APE/Ref-1 is a key regulator, it markedly induces and efficiently protects melanocytes from oxidative damage by inducing the antiapoptotic machinery and stimulating cell survival
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additional information
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APE1 can incise DNA at the 5'-position of oxidized pyrimidine bases such as 5,6-dihydro-thymine or 5,6-dihydro-2'-deoxyuracil (DHU), thus initiating a repair process known as nucleotide incision repair (NIR)
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additional information
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APE1 has DNA 3'-phosphatase activity in vitro and 3' to 5' exonuclease activity, which could be physiologically relevant in the removal of mismatched or damaged nucleotides incorporated during the synthesis step of BER
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additional information
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Ape1 has the ability to incise at AP sites in DNA conformations formed during DNA replication, transcription, and class switch recombination, and that Ape1 can endonucleolytically destroy damaged RNA
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additional information
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Ape1 is a multifunctional enzyme of 318 amino acids with redox-dependent regulation of transcription factors, 3' to 5' exonuclease, 3' phosphodiesterase, RNaseH and class II type AP endonuclease activities
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additional information
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APE1 is also named as redox effector factor-1 because of its redox abilities on different redox-regulated transcription factors
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additional information
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APE1/Ref-1 also has a complex relationship to high-mobility group box 1, a protein secreted by immune cells in response to inflammatory stimuli. APE1/Ref-1 can both promote and suppress inflammatory signaling induced by high-mobility group box 1
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additional information
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APE1/Ref-1 plays a complex role in the activation of nuclear factor kappa B, a key transcription factor involved in inflammatory and immune signaling
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additional information
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APE1/Ref-1 plays a role in cardiovascular physiology and pathophysiology. APE1/Ref-1 suppresses myocardial ischemia-reperfusion injury and vascular inflammation, and promotes endothelium-dependent vascular relaxation
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additional information
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APE1/Ref-1 promotes the effect of angiotensin II on Ca2+-activated K+-channel in human endothelial cells via suppression of NADPH oxidase
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additional information
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APE1/Ref-1 reduces oxidative stress by regulating the level of reactive oxygen species in the cytoplasm
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additional information
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APEs have 2 intrinsic activities in DNA repair. They act as an endonuclease in cleaving AP sites to generate 3' OH and 5' phosphodeoxyribose termini. They also act as a 3' phosphodiesterase/exonuclease to remove 3' blocking phosphodeoxyribose or its fragments generated during strand breaks, and by reactive oxygen species or DNA glycosylases that excise oxidized bases in the first step of base excision repair
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additional information
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enzyme cleaves the AP sites in DNA and allows them to be repaired by other enzymes involved in base excision repair
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additional information
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enzyme has an essential base excision repair (BER) activity and a redox activity that regulates expression of a number of genes through reduction of their transcription factors, AP-1, NFkappaB, HIF-1alpha, CREB, p53 and others
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additional information
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enzyme has the ability to reductively activate redoxsensitive transcription factors and negative gene regulation by extracellular calcium
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additional information
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enzyme stimulates the DNA binding activity of the AP-1 family of transcription factors via a redox-dependent mechanism
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additional information
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forced cytoplasmic overexpression of APE1 profoundly attenuates the upregulation of high-mobility group box 1-mediated reactive oxygen species generation, cytokine secretion, and cyclooxygenase-2 expression by primary monocytes and macrophage-like THP-1 cell lines
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additional information
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high-mobility group box 1-induced activation of p38 and c-Jun N-terminal kinase is strongly abrogated by the overexpression of APE1
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additional information
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hNTH1 and Y-box-binding protein-1 may be part of the same DNA repair pathway in response to cisplatin and UV treatments
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additional information
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hNTH1 binds directly to Y-box-binding protein-1 in the absence of nucleic acids, it binds to the auto-inhibitory n-terminal tail of NTH1
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additional information
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human Ape1 is a multifunctional protein with a major role in initiating repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage
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additional information
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human apurinic/apyrimidinic endonuclease 1 is a major constituent of the base excision repair (BER) pathway of AP sites of DNA lesions. APE1 specifically binds to abasic sites and cuts the 5'-phosphodiester bond with its endonuclease activity to produce a DNA primer with 3'-hydroxyl end, which is a required step in the BER repair pathway
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additional information
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human endonuclease III is a relevant target to potentiate cisplatin cytotoxicity in Y-box-binding protein-1 overexpressing tumor cells
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additional information
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In addition to the exonuclease function, human APE1 is endowed with another enzymatic activity potentially relevant for the protection against oxidative damage
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additional information
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In human cells, APE1 excises sugar fragments that block the 3'-ends thus facilitating DNA repair synthesis
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additional information
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major factor in the maintenance of the integrity of the human genome
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additional information
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multifunctional protein involved in base excision DNA repair and in transcriptional regulation of gene expression, importance to genomic stability and cell survival
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additional information
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multifunctional protein involved in reduction-oxidation regulation. It functions as a redox factor that maintains transcription factors in an active reduced state
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additional information
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overexpression of APE1/Ref-1 suppressed angiotensin II induced production of superoxide and hydrogen peroxide
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additional information
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small interfering RNA knockdown of endogenous APE1 impairs high-mobility group box 1-mediated cytokine expression and MAPK activation in THP-1 cells. High-mobility group box 1-stimulation induces the translocation of APE1 to the nucleus of the cell
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additional information
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The BK-Ca current in APE1/Ref-1-overexpressing human umbilical vein endothelial cells is similarly inhibited by angiotensin II, except that inhibition of 43.06% is achieved using only 10 nM angiotensin II
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additional information
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the DNA-binding ability of NF-kappaB in the Ape1/Ref-1 expressing cells is significantly increased
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additional information
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the key function is to produce a 3' OH terminus that serves as a primer for repair synthesis.
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additional information
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ubiquitously expressed protein that functions as both an endonuclease in the repair of oxidatively damaged DNA and an aid in the binding of redox-sensitive transcription factors
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
Co2+
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CoCl2 (500 microM) is essential for AP endonuclease assay. Effects of Co on APE/Ref-1 are concentration dependent
Fe
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pro-inflammatory activity of iron in the lung injury, at least in part, because of its induction of APE/Ref-1
Fe2+
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Fe2+ is able to support the incision activity of the enzyme at excess protein to DNA ratios of at least 6:1, Mg2+ and Fe2+ compete for the same metal-binding site
Iron
K+
KCl
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maximal AP endonuclease activity at 25-200 mM, nucleotide incision repair activity decreases dramatically above 50 mM
Mg2+
MgCl2
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tetrahydrofuran*G incision is efficiently catalyzed at 0.001 mM Mg2+, 5 mM MgCl2 are required for optimal AP endonuclease activity
Mn2+
Sm2+
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the divalent metal ion soaked with the protein crystals is found specifically to associate with the glutamate residue
additional information
Mg2+
APE1 binds to AP sites in the absence of Mg2+, a condition in which APE1 does not have endonuclease activity
Mg2+
binds to APE1 and a functional APE1-substrate DNA complex with an overall stoichiometry of one Mg2+ per mole of APE1, the chemistry central to the function of APE1 is water activated by a Mg2+ ion, Mg2+ binding is an absolute requirement for the endonucleolytic activity
Mg2+
required. Increasing the Mg2+ concentration alters the ratio of turns to beta-strands, and this change may be associated with the conformational changes required to achieve an active state
Mg2+
activates, Mg2+ or Mn2+ is required for endonuclease and exonuclease activity of APE1. Mg2+ is required for both binding of the protein with DNA and cleavage of phosphodiester bond catalyzed by APE1. Depending on the Mg2+ concentration, the limiting stage of the process can change
Mg2+
activates, required and involved in catalytic mechanism, Mg2+ ions stabilize the protein structure and the enzyme-substrate complex. Analysis of enzyme-substrate complexes with bound Mg2+
Mn2+
activates, Mg2+ or Mn2+ is required for endonuclease and exonuclease activity of APE1
K+
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both MgCl2 and KCl strongly influence the efficiency of Ape1 as an ssDNA or dsDNA AP endonuclease
K+
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K+ significantly stimulates recombinant APE1 activity at 20 mM by approximately 1.3fold (compared with the absence of K+)
Mg2+
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repair of 5-OH-C opposite guanine is stimulated 2-fold with increasing concentrations, 5-OH-C paired with adenine is poorly repaired with increasing Mg2+ concentrations, no incision of 5-OH-C opposite adenine above 15 mM Mg2+
Mg2+
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APE1 reaches a maximum of 3'-phosphoglycolate excision activity at Mg2+ concentrations around 2.5 mM, APE1 mutant D70A reaches maximum activity at higher metal concentrations. In case of a THF-containing oligonucleotide as substrate, APE1 exhibits the highest AP endonuclease activity at 5 mM of metal while the specific activity of APE1 mutant D70A did not reach a maximum until 40 mM of Mg2+ is added to the reaction.
Mg2+
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In presence of Mg2+, ATP has complex effects on Ape1 cleavage activity. Endo- and exonuclease activity of Ape1 is found to be influenced by the MgCl2 concentration, with optimal exonuclease activity at low MgCl2 concentration (0.1-2 mM) and optimal endonuclease activity at high MgCl2 concentration (10-15 mM).
Mg2+
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Mg2+, with potential binding sites A and B, binds at the B site of wild-type APE1-substrate complex and moves to the A site after cleavage occurs
Mg2+
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ion concentrations ranging from 0.2 to 2 mM Mg2+ promotes catalysis, APE1 is enhanced approximately 2fold (compared with the absence of Mg2+) in the presence of 2 mM Mg2+
Mg2+
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both the endoribonuclease and the ssRNA apurinic/apyrimidinic site cleavage activities of wild-type APE1 are present in the absence of Mg2+, while ssDNA apurinic/apyrimidinic site cleavage requires Mg2+, optimally at 0.5-2.0 mM
additional information
effects of monovalent (K+) and divalent (Mg2+, Mn2+, Ca2+, Zn2+, Cu2+, and Ni2+) metal ions on DNA binding and catalytic stages, circular dichroism spectra and calculation of the contact area between APE1 and DNA, overview. The first step of substrate binding (corresponding to formation of a primary enzyme-substrate complex) does not depend on the concentration (0.05-5.0 mM) or the nature of divalent metal ions. In contrast, the initial DNA binding efficiency significantly decreases at a high concentration (5-250 mM) of monovalent K+ ions, indicating the involvement of electrostatic interactions in this stage. The enzymatic activity of APE1 is increased in the ascending order Zn2+, Ni2+, Mn2+, and Mg2+
additional information
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effects of monovalent (K+) and divalent (Mg2+, Mn2+, Ca2+, Zn2+, Cu2+, and Ni2+) metal ions on DNA binding and catalytic stages, circular dichroism spectra and calculation of the contact area between APE1 and DNA, overview. The first step of substrate binding (corresponding to formation of a primary enzyme-substrate complex) does not depend on the concentration (0.05-5.0 mM) or the nature of divalent metal ions. In contrast, the initial DNA binding efficiency significantly decreases at a high concentration (5-250 mM) of monovalent K+ ions, indicating the involvement of electrostatic interactions in this stage. The enzymatic activity of APE1 is increased in the ascending order Zn2+, Ni2+, Mn2+, and Mg2+
additional information
there is only one bivalent metal ion in the APE1 active site present in the crystal formed at pH 4.6. In the structure produced at pH 7.5, i.e. under conditions optimal for endonuclease activity, two metal ions are located in the active site of the enzyme. MgCl2 concentration in the range 0.5-2.0 mM and low (50 mM or below) concentration of KCl are optimal for cleavage of single-stranded DNA with an AP site, while the endonuclease activity towards the double-stranded AP-DNA is the highest at 10 mM MgCl2 and 50 mM KCl or 2 mM MgCl2 and 200 mM KCl. Co2+ and Ni2+ do not affect APE1 activity
additional information
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there is only one bivalent metal ion in the APE1 active site present in the crystal formed at pH 4.6. In the structure produced at pH 7.5, i.e. under conditions optimal for endonuclease activity, two metal ions are located in the active site of the enzyme. MgCl2 concentration in the range 0.5-2.0 mM and low (50 mM or below) concentration of KCl are optimal for cleavage of single-stranded DNA with an AP site, while the endonuclease activity towards the double-stranded AP-DNA is the highest at 10 mM MgCl2 and 50 mM KCl or 2 mM MgCl2 and 200 mM KCl. Co2+ and Ni2+ do not affect APE1 activity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione
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(2E)-2-(3,4-dihydroxybenzoyl)-3-(3,4-dihydroxyphenyl)prop-2-enenitrile
-
(2E)-2-methyl-3-[3-(methylsulfanyl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl]prop-2-enoic acid
-
(2E)-2-[(3-bromo-1,4-dioxo-1,4-dihydronaphthalen-2-yl)methylidene]-4-methoxybutanoic acid
-
(2E)-2-[(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)methylidene]-4-methoxybutanoic acid
-
(2E)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylidene]-N-methoxydodecanamide
i.e. E3330-amide
(2E)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylidene]dodecanoic acid
i.e. E3330
(2E)-3-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)-2-methylprop-2-enoic acid
-
(2E)-3-(2-chloro-4,5-dimethoxy-3,6-dioxocyclohexa-1,4-dien-1-yl)-2-methylprop-2-enoic acid
-
(2E)-3-(3-bromo-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-2-methylprop-2-enoic acid
-
(2E)-3-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-2-methylprop-2-enoic acid
-
(2E)-3-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-N-(2-hydroxyethyl)-2-methylprop-2-enamide
-
(2E)-3-(3-methoxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-2-methylprop-2-enoic acid
-
(2E)-3-[3-[dihydroxy(oxido)-lambda5-stibanyl]phenyl]prop-2-enoic acid
-
(2R)-1-(1-benzofuran-2-yl)-2-(1,3-benzothiazol-2-yl)-2-hydroxyethanone
-
(3-chloro-1-benzothiophen-2-yl)[(2Z)-2-[(2-chlorophenyl)imino]-4-methylidene-3-thia-1-azaspiro[4.5]dec-1-yl]methanone
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(3a'S,6a'R)-5'-(1,3-benzodioxol-5-ylmethyl)-3'-(2-carboxyethyl)-7-chloro-2,4',6'-trioxo-1,2,3',3a',4',5',6',6a'-octahydro-2'H-spiro[indole-3,1'-pyrrolo[3,4-c]pyrrol[2]ium]
-
(5E)-1-(furan-2-ylmethyl)-5-[(2E)-3-(furan-2-yl)prop-2-en-1-ylidene]pyrimidine-2,4,6(1H,3H,5H)-trione
-
(5R)-4-hydroxy-3,5-dimethyl-5-((2S)-3-methylpent-4-en-2-yl)thiophen-2(5H)-one
-
1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)-2,2'-binaphthalene-8,8'-dicarbaldehyde
-
1,4-dihydroxy-5,8-bis([2-[(2-hydroxyethyl)amino]ethyl]amino)anthracene-9,10-dione
-
1,6,6-trimethyl-6,7,8,9-tetrahydrophenanthro[1,2-b]furan-10,11-dione
-
1-amino-4-[[4-([4-chloro-6-[(4-sulfophenyl)amino]-1,3,5-triazin-2-yl]amino)phenyl]amino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonic acid
-
1-methyl-4-[(1E)-1-[2-(6-methyl[1,3]dioxolo[4,5-g]quinolin-8-yl)hydrazinylidene]ethyl]-2-phenyl-1,2-dihydro-3H-pyrazol-3-one
1-[3-[(6-chloro-2-methoxyacridin-9-yl)amino]propyl]-3-[3-(2,6-diamino-9H-purin-9-yl)propyl]guanidine
-
1-[4-[(6-chloro-2-methoxyacridin-9-yl)amino]butyl]-3-[4-(2,6-diamino-9H-purin-9-yl)butyl]guanidine
-
1-[[2-(ethylamino)ethyl]amino]-4-(hydroxymethyl)-9H-thioxanthen-9-one
-
10,12-dimethyl-2-(propan-2-yl)-6H-[1,3]oxazolo[4,5-g]pyrido[4,3-b]carbazol-10-ium
-
2,2'-(3,7-dioxo-5,7-dihydro-1H,3H-benzo[1,2-c:4,5-c']difuran-1,5-diyl)diacetic acid
-
2-((Z)-2-oxo-3-(4-oxo-2-thioxothiazolidin-5-ylidene)indolin-1-yl)acetic acid
potent inhibitory activity
2-(4-chlorophenyl)-4-(2'-fluorobiphenyl-4-yl)-5-methyl-1,3-thiazole
-
2-(5-((2-(2-carboxyphenyl)-1,3-dioxo)-2,3-dihydro-1H-isoindol-5-yl)carbonyl}-1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)benzoic acid
potent inhibitory activity
2-(carboxymethyl)-4-([4-[(4-carboxyphenyl)sulfanyl]phenyl]sulfonyl)benzoic acid
-
2-amino-3-(3-[2-amino-1-[2-(6-amino-9H-purin-9-yl)ethyl]triaz-2-en-2-ium-1-yl]propyl)-3-[3-[(6-chloro-2-methoxyacridin-9-yl)amino]propyl]triaz-1-en-2-ium
-
2-[(5R)-3-(naphthalen-2-yl)-5-phenyl-2,5-dihydro-1H-pyrazol-1-yl]-2-oxoethyl 5-nitrothiophene-2-carboxylate
-
2-[(5Z)-5-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
2-[(Z)-(4-hydroxy-3-methylphenyl)(3-methyl-4-methylidenecyclohexa-2,5-dien-1-ylidene)methyl]benzoic acid
-
2-[5-[1-(carboxymethyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
3,3'-[(3-carboxy-4-oxocyclohexa-2,5-dien-1-ylidene)methanediyl]bis(6-hydroxybenzoic acid)
-
3-(1-(carboxymethyl)-5-(4-chlorophenyl)-1H-pyrrol-2-yl)propanoic acid
potent inhibitory activity
3-(1-(carboxymethyl)-5-(4-fluorophenyl)-1H-pyrrol-2-yl)propanoic acid
potent inhibitory activity
3-(1-(carboxymethyl)-5-(thiophen-2-yl)-1H-pyrrol-2-yl)propanoic acid
potent inhibitory activity
3-(5-((E)-(3-(carboxymethyl)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl)furan-2-yl)benzoic acid
potent inhibitory activity
3-[(4Z)-4-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-5-oxo-2-thioxoimidazolidin-1-yl]propanoic acid
-
3-[1-(carboxymethyl)-5-(4-chlorophenyl)-1H-pyrrol-2-yl]propanoic acid
-
3-[4-[(3aR,9bR)-9-methoxy-1,3a,4,9b-tetrahydrochromeno[3,4-c]pyrrol-2(3H)-yl]butyl]-8-phenylpyrazino[2',3':4,5]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione
-
3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2-propionic acid
E3330 specifically blocking the APE1 redox but not DNA activity, an equilibrium constant (KD) of 1.6 nM is obtained for the binding of E3330 to APE1. E3330 is also shown to block the ability of APE1 to reduce NF-kappaB, thus interfering with the redox activity of APE1
3-[[4-(carboxymethyl)benzyl]sulfanyl]-8-methyl-5H-[1,2,4]triazino[5,6-b]indole-5-carboxylic acid
-
4'-(2-chloro-6-nitrophenoxy)biphenyl-4-yl 4-tert-butylbenzenesulfonate
-
4-((2-carboxyphenoxy)methyl)-2,5-dimethylfuran-3-carboxylic acid
potent inhibitory activity
4-(4-(4-carboxyphenylsulfonyl)phenyl)sulfanylbenzene-1,2-dioic acid
potent inhibitory activity
4-(4-(4-carboxyphenylthio)phenylsulfonyl)benzene-1,2-dioic acid
potent inhibitory activity
4-([[(3-carboxy-5-methylfuran-2-yl)methyl]sulfanyl]methyl)-5-methylfuran-2-carboxylic acid
-
4-benzyl-1-(3-[[(3-nitrophenyl)sulfonyl]amino]quinoxalin-2-yl)pyridinium
-
4-[(4Z)-4-([5-[4-chloro-3-(ethoxycarbonyl)phenyl]furan-2-yl]methylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
4-[(4Z)-4-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-5-oxo-2-thioxoimidazolidin-1-yl]butanoic acid
-
5,5'-[ethane-1,2-diylbis(sulfanediylmethanediyl)]bis(2-methylfuran-3-carboxylic acid)
-
5,5'-[methanediylbis(sulfanediylmethanediyl)]bis(2-methylfuran-3-carboxylic acid)
-
5-(((tetrahydrofuran-2-yl)methylthio)methyl)-2-methylfuran-3-carboxylic acid
-
5-(acetylamino)-2-[(E)-2-(4-isothiocyanato-3-sulfophenyl)ethenyl]benzenesulfonic acid (non-preferred name)
-
5-(acetylamino)-2-[2-(4-isothiocyanato-3-sulfophenyl)ethenyl] benzenesulfonic acid
shows no cytotoxicity in MCF10A cells
5-([[(4-carboxy-5-methylfuran-2-yl)methyl]sulfanyl]methyl)-3-methylfuran-2-carboxylic acid
-
5-[4-[(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl)methoxy]benzyl]-1,3-thiazolidine-2,4-dione
-
6-amino-4-hydroxy-5-[(4-nitro-2-sulfophenyl)azo]-2-naphtalenesulfonic acid
shows no cytotoxicity in MCF10A cells
6-amino-4-hydroxy-5-[(E)-(4-nitro-2-sulfophenyl)diazenyl]naphthalene-2-sulfonic acid
-
6-amino-5-[(4-amino-2-sulfophenyl)azo]-4-hydroxy-2-naphtalenesulfonic acid
shows no cytotoxicity in MCF10A cells
6-amino-5-[(E)-(4-amino-2-sulfophenyl)diazenyl]-4-hydroxynaphthalene-2-sulfonic acid
-
8-[(2E)-2-(1,3-benzodioxol-5-ylmethylidene)hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
-
8-[(2E)-2-(3-methoxybenzylidene)hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
inhibitor induces time-dependent increases in the accumulation of abasic sites in cells at levels that correlate with its potency to inhibit APE-1 endonuclease excision. The inhibitor also potentiates by 5fold the toxicity of a DNA methylating agent that creates abasic sites
8-[(2E)-2-[(9-ethyl-9H-carbazol-3-yl)methylidene]hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
8-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-1-thia-4,8-diazaspiro[4.5]decan-3-one
-
Ca2+
Ca2+ cause a complete loss of catalytic activity of APE1 with retention of binding potential
Cu2+
Cu2+ ions abrogate the DNA binding ability of APE1, possibly, due to a strong interaction with DNA bases and the sugar-phosphate backbone
K+
initial DNA binding efficiency significantly decreases at a high concentration (5-250 mM) of monovalent K+ ions
N-(3,5-dichlorophenyl)-4-(2'-fluorobiphenyl-4-yl)-5-methyl-1,3-thiazol-2-amine
-
N-(3-chlorophenyl)-5,6-dihydro-4H-cyclopenta[d][1,2]oxazole-3-carboxamide
-
N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)-2-(1H-1,2,4-triazol-5-ylsulfanyl)acetamide
-
N-benzyl-2-(3-cyanophenyl)-1,3,7-trioxo-2,3,7,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-5-carboxamide
-
N-[3-(1,3-benzothiazol-2-yl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl]acetamide
-
N-[3-(1,3-benzothiazol-2-yl)-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl]acetamide
-
N-[3-(1,3-benzothiazol-2-yl)-6-(propan-2-yl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl]acetamide
-
N-[3-(4-phenyl-1,3-thiazol-2-yl)-6-(propan-2-yl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl]acetamide
-
nucleotides
dAMP across from the AP site does not cause any distortions in the helix in comparison with the undamaged DNA, while the presence dCMP and dGMP results in changes in the helical structure to a varying degree providing out-of-helix position of the nucleotide and/or AP site
-
RPA proteins
RPA proteins are able to suppress the APE1 endonuclease activity in ssDNA of a replicative fork but not in a transcription bubble or in dsDNA
-
tetrahydrofuran-2-ylmethyl 6-(furan-2-yl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carboxylate
-
[(3Z)-3-(3-[[(2-hydroxyphenyl)carbonyl]amino]-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)-2-oxo-2,3-dihydro-1H-indol-1-yl]acetic acid
-
[(3Z)-3-[3-(4-bromophenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]-2-oxo-2,3-dihydro-1H-indol-1-yl]acetic acid
-
[(5Z)-5-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
2,4,9-trimethylbenzo[b][1,8]naphthyridin-5-amine
-
i.e. Ape1 repair inhibitor 03, specific inhibitor of AP endonuclease
2-(4-(2,5-dimethyl-1H-prryol-1-yl)phenoxy) acetic acid
-
i.e. Ape1 repair inhibitor 01, specific inhibitor of AP endonuclease
4-(2,6,8-trimethylquinolin-4-ylamino)phenol
-
i.e. Ape1 repair inhibitor 02, specific inhibitor of AP endonuclease
7-nitro-1H-indole 2-carboxylic acid
-
CRT0044876, binds to the active site of APE/Ref-1 and effectively inhibits its AP endonuclease, 3'-phosphodiesterase and 3'-phosphatase activities at low micromolar concentrations
ATP
-
in presence of 1 mM Mg2+, Ape1 incision activity is inhibited at higher ATP concentrations (2-5 mM). Depending on the relative concentration of Mg2+, ATP can have both inhibitory and stimulatory consequences on Ape1 incision capacity
Harmane
-
i.e. 1-methyl-9H-pyrido-[3,4-b]indole, only slight inhibition of AP endocunlease I and II
isoflavones
-
soy isoflavones decrease apurinic/apyrimidinic endonuclease 1/redox factor-1 expression
K+
-
K+ is inhibitory to the native APE1 at 0.2-10 mM with approximately 5fold inhibition
lucanthone
-
inhibits repair activity from cellular extracts and enhances cell killing effect of the laboratory alkylating agent methyl methanesulfonate and the clinically relevant agent temozolomide, no inhibition of redox function or exonuclease activity on mismatched nucleotides
N-(3-chlorophenyl)-5,6-dihyro-4H-cyclopenta[d]isoxazole-3-carboxamide
-
i.e. Ape1 repair inhibitor 06, specific inhibitor of AP endonuclease
P53
-
after camptothecin treatment, p53 is a negative regulator of APE1 expression, APE1 promoter activity is repressed by wild-type p53, but not by mutant p53
polyinosinic-polycytidylic acid
-
transfection of APE1 suppresses the extracellular release of high-mobility group box 1 in response to polyinosinic-polycytidylic acid stimulation
-
proteinBcl2
-
overexpression of Bcl2, a major cellular oncogenic protein, in cells reduces formation of the APE1-XRCC1 complex, Bcl2 not only prolongs cell survival but also suppresses the repair of abasic (AP) sites of DNA lesions. Bcl2 directly interacts with APE1 via its BH domains, and deletion of any of the BH domains from Bcl2 results in loss of the ability of Bcl2 to suppress APE1 endonuclease activity and AP site repair
-
reactive oxygen species
-
reactive oxygen species not only can inhibit APE/Ref-1 activities by direct oxidation of amino acid residues, but also affects the expression level and subcellular localization of APE/Ref-1
-
resveratrol
-
dock into one of the two drug-treatable pockets located in the redox domain
1-methyl-4-[(1E)-1-[2-(6-methyl[1,3]dioxolo[4,5-g]quinolin-8-yl)hydrazinylidene]ethyl]-2-phenyl-1,2-dihydro-3H-pyrazol-3-one
-
1-methyl-4-[(1E)-1-[2-(6-methyl[1,3]dioxolo[4,5-g]quinolin-8-yl)hydrazinylidene]ethyl]-2-phenyl-1,2-dihydro-3H-pyrazol-3-one
inhibitor induces time-dependent increases in the accumulation of abasic sites in cells at levels that correlate with its potency to inhibit APE-1 endonuclease excision. The inhibitor also potentiates by 5fold the toxicity of a DNA methylating agent that creates abasic sites
2,2'-[butane-1,4-diylbis(1H-benzimidazole-2,1-diyl)]diacetic acid
-
7-nitro-1H-indole-2-carboxylic acid
CRT0044876, a direct inhibitor of the DNA repair activity of APE1
8-[(2E)-2-[(9-ethyl-9H-carbazol-3-yl)methylidene]hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
-
8-[(2E)-2-[(9-ethyl-9H-carbazol-3-yl)methylidene]hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
inhibitor induces time-dependent increases in the accumulation of abasic sites in cells at levels that correlate with its potency to inhibit APE-1 endonuclease excision. The inhibitor also potentiates by 5fold the toxicity of a DNA methylating agent that creates abasic sites
methoxyamine
methoxyamine (CH3ONH2) specifically inhibits virtually all AP endonucleases, irrespective of their action modes
methoxyamine
MX, an indirect inhibitor. MX increases the cytotoxicity of chemotherapeutic drugs such as temozolomide, carmustine, pemetrexed, and 5-iodo-2'-deoxyuridine in preclinical models
methoxyamine
treatment completely abrogates APE1 acetylation in a dose- and time-dependent manner. Methoxyamine (MX) covalently binds to AP sites to form methoxyamine-bound AP (MX-AP) sites and competitively inhibits the binding of APE1 to AP sites. These MX-AP sites are resistant to recognition and repair by APE1
E3330
-
forms a reversible adduct with DELTA40APE1, an N-terminal truncation of APE1 including residues 40-318. E3330 also increases the extent of disulfide bond formation involving redox critical Cys residues in APE1
KCl
-
maximal AP endonuclease activity at 25-200 mM, nucleotide incision repair activity decreases dramatically above 50 mM
KCl
-
varying concentrations of KCl show an initial decrease followed by a significant increase in KD value for the APE/AP DNA binding
Mg2+
-
AP-endonuclease activity of the C99S mutant as well as of the double mutants C138S/C99S and C65S/C99S is strongly inhibits in the presence of 10 mM Mg2+. Increasing Mg2+ concentration to 10 mM inhibited product formation by 5.4-fold. At 20 mM Mg2+, the product formation with wild-type APE1 is inhibited 4.2-fold and with the C99S mutant 14-fold relative to the activity of the wild-type protein in 5 mM Mg2+
Mg2+
-
In case of APE 1, the excision being severely inhibited (below 25%) at 10 mM and higher ion concentrations. APE1 mutant D70A is more refractory to Mg2+ inhibition, thus still retaining about 50% of activity at 20 mM Mg2+. In case of a THF-containing oligonucleotide as substrate, inhibition is not evidenced until 80mM is reached.
N-ethylmaleimide
-
treatment of fully denatured full-length APE1 and DELTA40APE1, an N-terminal truncation of APE1 including residues 40-318, results in modification of 7 and 2 resiudes, respectively
additional information
analysis of enzyme activity and kinetics with DNA substrates comprising duplexes of deoxyribonucleotides with one 5'-dangling end that contain a fluorescent 2-aminopurine residue at the 1st, 2nd, 4th, or 6th position from the 3'-end of the short oligonucleotide. The impact of the 3'-end nucleotide, which contains mismatched, undamaged bases or modified bases as well as an abasic site or phosphate group, on the efficiency of 3'-5'-exonuclease activity is determined
-
additional information
-
analysis of enzyme activity and kinetics with DNA substrates comprising duplexes of deoxyribonucleotides with one 5'-dangling end that contain a fluorescent 2-aminopurine residue at the 1st, 2nd, 4th, or 6th position from the 3'-end of the short oligonucleotide. The impact of the 3'-end nucleotide, which contains mismatched, undamaged bases or modified bases as well as an abasic site or phosphate group, on the efficiency of 3'-5'-exonuclease activity is determined
-
additional information
association of APE1 with undamaged DNA reduces effective concentration of the enzyme and subsequently decreases APE1-catalyzed cleavage rates on long DNA substrates
-
additional information
-
association of APE1 with undamaged DNA reduces effective concentration of the enzyme and subsequently decreases APE1-catalyzed cleavage rates on long DNA substrates
-
additional information
bis-naphthalene macrocycles, which bind with high affinity and selectivity to abasic sites in DNA, efficiently inhibit their cleavage by APE1 (IC50 value is 55-60 nM in the kinetic assay with a model THF substrate). Substrate masking by non-covalent abasic-site ligands is an efficient strategy for inhibition of APE1. Inhibition of abasic site-specific endonuclease activity of nuclear extracts and gel-based assays for APE1 inhibition
-
additional information
-
bis-naphthalene macrocycles, which bind with high affinity and selectivity to abasic sites in DNA, efficiently inhibit their cleavage by APE1 (IC50 value is 55-60 nM in the kinetic assay with a model THF substrate). Substrate masking by non-covalent abasic-site ligands is an efficient strategy for inhibition of APE1. Inhibition of abasic site-specific endonuclease activity of nuclear extracts and gel-based assays for APE1 inhibition
-
additional information
identification of small molecule inhibitors against APE1/Ref-1 activities, structures and activities of APE1/Ref-1 inhibitors, that target both DNA repair and redox activities, molecular docking, overview
-
additional information
identification of small molecule inhibitors against APE1/Ref-1 activities, structures and activities of APE1/Ref-1 inhibitors, that target both DNA repair and redox activities, molecular docking, overview
-
additional information
-
identification of small molecule inhibitors against APE1/Ref-1 activities, structures and activities of APE1/Ref-1 inhibitors, that target both DNA repair and redox activities, molecular docking, overview
-
additional information
preparation of modified oligonucleotide derivatives as unreactive substrate analogues of human apurinic/apyrimidinic endonuclease APE1 for rational design of enzyme inhibitors or as potential APE1 inhibitors themselves. The 3'-terminal internucleotide phosphate group is chemically modified by the replacement of its oxygen atom by either a sulphur or a Tmg group to make the phosphate resistant to the exonuclease activity of the enzyme. Instead of the natural AP-site, the oligonucleotides incorporate its chemically stable analogue (2R,3S)-2-(hydroxymethyl)-3-hydroxytetrahydrofuran (F-site). It is known that such a substitution scarcely affects the activity of APE1. Structure of the F-site and chemical modifications of the phosphate group on its 5'-side that are resistant to APE1 hydrolysis, overview. The endonuclease activity of APE1 is considerably retarded for DNA duplexes containing phosphate modifications on the 5'-side of the F-site. But analysis of the products of chain scission of those duplexes reveals that some 3'-5'-exonuclease reaction, that removes the 3'-terminal nucleotide, also occurs. To suppress the removal of the 3'-terminal nucleotide from the model oligonucleotides, their 3'-terminal internucleotide phosphate group is modified. The tetramethyl phosphoryl guanidine group (Tmg) is employed as a nuclease-resistant phosphate group isostere. It is observed that such a modification blocks 3'-5'-exonuclease activity of APE1 for more than 12 h
-
additional information
-
preparation of modified oligonucleotide derivatives as unreactive substrate analogues of human apurinic/apyrimidinic endonuclease APE1 for rational design of enzyme inhibitors or as potential APE1 inhibitors themselves. The 3'-terminal internucleotide phosphate group is chemically modified by the replacement of its oxygen atom by either a sulphur or a Tmg group to make the phosphate resistant to the exonuclease activity of the enzyme. Instead of the natural AP-site, the oligonucleotides incorporate its chemically stable analogue (2R,3S)-2-(hydroxymethyl)-3-hydroxytetrahydrofuran (F-site). It is known that such a substitution scarcely affects the activity of APE1. Structure of the F-site and chemical modifications of the phosphate group on its 5'-side that are resistant to APE1 hydrolysis, overview. The endonuclease activity of APE1 is considerably retarded for DNA duplexes containing phosphate modifications on the 5'-side of the F-site. But analysis of the products of chain scission of those duplexes reveals that some 3'-5'-exonuclease reaction, that removes the 3'-terminal nucleotide, also occurs. To suppress the removal of the 3'-terminal nucleotide from the model oligonucleotides, their 3'-terminal internucleotide phosphate group is modified. The tetramethyl phosphoryl guanidine group (Tmg) is employed as a nuclease-resistant phosphate group isostere. It is observed that such a modification blocks 3'-5'-exonuclease activity of APE1 for more than 12 h
-
additional information
the cleavage of single-stranded DNA with an AP site does not depend on the presence of DNA glycosylases, and it is not inhibited by the reaction product. Replacement of tetrahydrofuran with a positively charged analogue pyrrolidine decreases endonuclease activity of the APE1 21fold and the DNA binding activity by 4fold. Endonuclease activity on DNA with an tetrahydrofuran residue decreases 7300fold in 4 mM EDTA in comparison with the activity in the presence of 10 mM Mg2+, and the activity decreases only 20-30fold on DNA containing ethane and propanediol in the center of the strand instead of an AP site
-
additional information
-
the cleavage of single-stranded DNA with an AP site does not depend on the presence of DNA glycosylases, and it is not inhibited by the reaction product. Replacement of tetrahydrofuran with a positively charged analogue pyrrolidine decreases endonuclease activity of the APE1 21fold and the DNA binding activity by 4fold. Endonuclease activity on DNA with an tetrahydrofuran residue decreases 7300fold in 4 mM EDTA in comparison with the activity in the presence of 10 mM Mg2+, and the activity decreases only 20-30fold on DNA containing ethane and propanediol in the center of the strand instead of an AP site
-
additional information
the enzyme is a promising target for the development of small-molecule inhibitors to be used in combination with anticancer agents, structure-based virtual library screening study based on compounds molecular docking analysis, overview. Compounds 5-(acetylamino)-2-[2-(4-isothiocyanato-3-sulfophenyl)ethenyl] benzenesulfonic acid, 6-amino-4-hydroxy-5-[(4-nitro-2-sulfophenyl)azo]-2-naphtalenesulfonic acid, and 6-amino-5-[(4-amino-2-sulfophenyl)azo]-4-hydroxy-2-naphtalenesulfonic acid appear to be important scaffolds for the design of novel APE1 inhibitors. Docking study uses the APE1 enzyme crystal structure, PDB ID 1BIX. All assayed molecules fit well within the APE1-binding site, occupying the pocket defined by the amino acids Asp70, Glu96, Arg177, His309, Asp210, Asn212, Trp280, Phe266, and Leu282. Evaluation of the cytotoxicity of potential APE1 inhibitors in MCF10A cells
-
additional information
-
the enzyme is a promising target for the development of small-molecule inhibitors to be used in combination with anticancer agents, structure-based virtual library screening study based on compounds molecular docking analysis, overview. Compounds 5-(acetylamino)-2-[2-(4-isothiocyanato-3-sulfophenyl)ethenyl] benzenesulfonic acid, 6-amino-4-hydroxy-5-[(4-nitro-2-sulfophenyl)azo]-2-naphtalenesulfonic acid, and 6-amino-5-[(4-amino-2-sulfophenyl)azo]-4-hydroxy-2-naphtalenesulfonic acid appear to be important scaffolds for the design of novel APE1 inhibitors. Docking study uses the APE1 enzyme crystal structure, PDB ID 1BIX. All assayed molecules fit well within the APE1-binding site, occupying the pocket defined by the amino acids Asp70, Glu96, Arg177, His309, Asp210, Asn212, Trp280, Phe266, and Leu282. Evaluation of the cytotoxicity of potential APE1 inhibitors in MCF10A cells
-
additional information
-
enzyme is inhibited by the product of its DNA N-glycosylase activity directed against Tg:G, the AP:G site, but not inhibited by the AP:A site arising from release of Tg from Tg:A
-
additional information
-
5-OH-C paired with adenine was poorly repaired with increasing Mg2+ concentrations, no incision of 5-OH-C opposite adenine above 15 mM Mg2+
-
additional information
-
in contrast to activity against abasic sites in souble-stranded DNA the enzyme does not display product inhibition when acting on absic sites in single-stranded DNA
-
additional information
-
the enzyme activity of apurinic/apyrimidinic endonuclease is blocked by APE-specific siRNAs
-
additional information
-
the enzyme activity of apurinic/apyrimidinic endonuclease is blocked by APE-specific siRNAs
-
additional information
-
APE1 silencing via siRNA transfection inhibits both the nuclear and cytoplasmic expression of APE1
-
additional information
-
hiolactomycin and methyl 3,4-dephostatin have no effect on total AP site cleavage activity
-
additional information
-
methoxyamine binds to and occludes abasic sites in DNA and thereby inhibits Ape1/Ref-1-mediated DNA repair
-
additional information
-
the presence within the G quadruplex DNA structure of an abasic site decreases the efficiency of human AP endonuclease activity. This effect is mostly the result of a decreased enzymatic activity and not of decreased binding of the enzyme to the damaged site
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cockayne syndrome B protein
cockayne syndrome B protein potentiates the APE1 activity on fully paired AP-DNA but much more on bubble AP-DNA, suggesting a role for this protein in the transcription-repair pathway
-
8-oxoguanine-DNA glycosylase
-
OGG1 stimulates the hydrolytic activity of AP endonuclease
-
APE1
-
APE1, a human homolog of Escherichia coli exonuclease III Xth stimulates under conditions of Vmax
-
ATP
-
in presence of 1 mM Mg2+, Ape1 abasic endonuclease activity is stimulated (1.75- and 1.25-fold at 0.5 and 1 mM ATP concentrations). At 10 mM MgCl2, the higher concentrations of ATP has stimulatory effects on AP site incision by Ape1
cisplatin
-
2fold increase in Y-box-binding protein-1/hNTH1 complex formation in transfected MCF-7 cells after a treatment of 12 microM cisplatin for 4 h
cockayne syndrome B protein
-
CSB protein stimulates the AP site incision activity of APE1
-
DNA-dependent ATPase CSB
-
in presence of 1 mM Mg2+, enzyme stimulates AP site incision by Ape1 in the absence of ATP on both fully paired duplex DNA (42F-42Comp) and an 11-nt bubble duplex substrate containing a centrally located abasic site (42F-42bubbleComp). When 2.5 mM ATP is included in the reactions with 1 mM MgCl2, inhibition of Ape1 incision activity is detected
-
Helicobacter pylori (CagA+) water-extract protein (HPWEP)
-
HPWEP-stimulation significantly increases APE-1 mRNA expression levels in human peripheral macrophages. HPWEP-stimulation increases APE-1 expression levels in AGS cells. HPWEP stimulation increases APE-1 protein expression in gastric epithelial MKN-28 cells in a dose-dependent manner (1:30 and 1:10 dilution). When normalized to beta-actin, HPWEP stimulation at a 1:10 dilution significantly increases APE-1 protein expression compared to control MKN-28 cells. APE-1 protein expression is further increased in HPWEP (1:10 dilution) stimulated MKN-28 cells after treatment with hypo/reoxygenation.
-
imidazole
-
enhances activity of wild-type enzyme markedly, enhances Y171A somewhat and fails to enhance Y171F. When stoichiometric levels of tyrosine are included in the reaction with imidazole, wild-type enzyme as well as mutant enzymes are stimulated. Degree of stimulation of wild-type enzyme continues to exceed that of the mutants
lipopolysaccharide
-
100 ng/ml lipopolysaccharide stimulates the upregulation and nuclear translocation of APE1 in activated macrophages. APE1 critically mediates both the translocation of NF-B to the nucleus and the expression of inducible nitric oxide synthase by murine macrophage RAW264.7 cells after stimulation with LPS
UV light
-
3fold increase in Y-box-binding protein-1/hNTH1 complex formation in transfected MCF-7 cells after a treatment with a UV irradiation dose of 40 J/m2 tested for 4 h
-
Y-box-binding protein-1
-
protein strongly stimulates in vitro the activity of hNTH1 toward DNA duplex probes containing oxidized bases, lesions prone to be present in cisplatin treated cells
-
KCl
-
varying concentrations of KCl show an initial decrease followed by a significant increase in KD value for the APE/AP DNA binding
additional information
APE1 functional activation is a consequence of different stimuli (UV light, hypoxia, ischemia/reperfusion, hypxic-ischemic insult, Helicobacter pylori infection, reactive oxygen species, atherosclerotic plaque, TSH, CD40 triggering, P2Y triggering, cysteamine-induced duodenal ulceration, Pb asbestos, intracellular Ca2+) that generate both physiological and toxic oxidative stress conditions or increase the intracellular cAMP levels leading to different outcomes
-
additional information
expression is altered in several metabolic and proliferative disorders such as in tumors and aging
-
additional information
functional triggering of membrane-bound receptors (such as those for thyrotropin, CD40L, ATP, interleukin-2) can lead to APE1 functional activation through intracellular generation of sublethal doses of reactive oxygen species
-
additional information
acetylation of APE1 enhances its AP catalytic efficiency. ANd APE1 acetylation enhances its interaction with downstream BER proteins and stability on chromatin
-
additional information
-
acetylation of APE1 enhances its AP catalytic efficiency. ANd APE1 acetylation enhances its interaction with downstream BER proteins and stability on chromatin
-
additional information
the 3'-5'-exonuclease activity of APE1 towards the DNA with a 5'-pFx02group is stimulated in the presence of PARP1
-
additional information
-
the 3'-5'-exonuclease activity of APE1 towards the DNA with a 5'-pFx02group is stimulated in the presence of PARP1
-
additional information
-
oxidative stress enhances enzyme activity by activation of the APE promoter
-
additional information
-
expression of AdAPE1/Ref-1 is significantly higher in cells transfected with AdAPE1/Ref-1 than in the control cells (5.3-fold) demonstrating that infection with AdAPE1/Ref-1 can significantly increase the amount of cytoplasmic APE1/Ref-1 in human umbilical vein endothelial cells
-
additional information
-
no increase in the amount of Y-box-binding protein-1/hNTH1 complex in transfected MCF-7 cells after camptothecin or mitomycin C treatments compared to untreated MCF7 cells
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00082
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
pH 7.5, 37°C
-
0.065
1-amino-4-(4-{(E)-[(4E)-6-chloro-4-[(3-sulfophenyl)imino]-3,4-dihydro-1,3,5-triazin-2(1H)-ylidene]amino}-3-sulfoanilino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonic acid
-
-
0.000098
12-mer oligodeoxyribonucleotide containing a tetrahydrofuran analogue at the natural AP site
-
wild-type, pH 7.5, 25°C
-
0.000424
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
-
recombinant enzyme
-
0.0000213
DNA containing apurinic/apyrimidinic site
-
pH 7.6, room temperature
-
0.0000084
duplex oligonucleotide containing a 5,6-dihydro-2'-deoxyuridine*G pair
-
pH 6.8, 37°C, nucleotide incison repair activity
-
0.0000072
duplex oligonucleotide containing a alpha-2'-deoxyadenosine*T pair
-
pH 6.8, 37°C, nucleotide incison repair activity
-
0.0000027
duplex oligonucleotide containing a tetrahydrofuran*G pair
-
pH 6.8, 37°C, nucleotide incison repair activity
-
0.0000034
43-mer oligonucleotide containing apurinic/apyrimidinic sites
37°C, wild-type enzyme
-
0.0000136
43-mer oligonucleotide containing apurinic/apyrimidinic sites
37°C, mutant enzyme N226A
-
0.0000184
43-mer oligonucleotide containing apurinic/apyrimidinic sites
37°C, mutant enzyme N229A
-
0.0000278
43-mer oligonucleotide containing apurinic/apyrimidinic sites
37°C, mutant enzyme N226A/N229A
-
0.000093
12-mer oligodeoxyribonucleotide containing a natural AP site
-
wild-type, pH 7.5, 25°C
-
0.00022
12-mer oligodeoxyribonucleotide containing a natural AP site
-
mutant Y171F/P173L/N174K, pH 7.5, 25°C
-
0.0000368
43-mer oligonucleotide containing the AP-site analog THF at nt 31
-
wild-type, presence of 2 mM Mg2+
-
0.0000536
43-mer oligonucleotide containing the AP-site analog THF at nt 31
-
mutant C99S, presence of 2 mM Mg2+
-
0.00000007
DNA containing 5-OH-C/A
-
wild-type, pH 7.5, 37°C, presence of EDTA
-
0.00000014
DNA containing 5-OH-C/A
-
P211R mutant, pH 7.5, 37°C, presence of Mg2+
-
0.0000002
DNA containing 5-OH-C/A
-
P211R mutant, pH 7.5, 37°C, presence of EDTA
-
0.0000017
DNA containing 5-OH-C/A
-
G212 mutant, pH 7.5, 37°C, presence of Mg2+
-
0.0000035
DNA containing 5-OH-C/A
-
G212 mutant, pH 7.5, 37°C, presence of EDTA
-
0.000000048
DNA containing 5-OH-C/G
-
P211R mutant, pH 7.5, 37°C, presence of Mg2+
-
0.00000005
DNA containing 5-OH-C/G
-
wild-type, pH 7.5, 37°C, presence of Mg2+ or EDTA
-
0.00000009
DNA containing 5-OH-C/G
-
P211R mutant, pH 7.5, 37°C, presence of EDTA
-
0.000001
DNA containing 5-OH-C/G
-
G212 mutant, pH 7.5, 37°C, presence of EDTA
-
0.0000012
DNA containing 5-OH-C/G
-
G212 mutant, pH 7.5, 37°C, presence of Mg2+
-
100
DNA containing an abasic site
-
pH 7.5, wild-type enzyme, low salt concentration (82 mM NaCl)
108
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y128A, high salt concentration (150 mM NaCl)
110
DNA containing an abasic site
-
pH 7.5, wild-type enzyme, high salt concentration (150 mM NaCl)
140
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y128A, low salt concentration (82 mM NaCl)
165
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y269A, low salt concentration (82 mM NaCl)
255
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171F, low salt concentration (82 mM NaCl)
310
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171A, high salt concentration (150 mM NaCl)
360
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171A, low salt concentration (82 mM NaCl)
413
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y269A, high salt concentration (150 mM NaCl)
0.000136
THF-containing oligonucleotide
-
APE1 mutant D70A, AP endonuclease activity
-
additional information
additional information
kinetic analysis of human 8-oxoguanine-DNA glycosylase activation through APE1, overview
-
additional information
additional information
-
kinetic analysis of human 8-oxoguanine-DNA glycosylase activation through APE1, overview
-
additional information
additional information
kinetic mechanism of 3'-end nucleotide removal in the 3'-5'-exonuclease process catalyzed by APE1 under pre-steady-state conditions, interaction of enzyme APE1 with DNA containing an abasic site, overview
-
additional information
additional information
-
kinetic mechanism of 3'-end nucleotide removal in the 3'-5'-exonuclease process catalyzed by APE1 under pre-steady-state conditions, interaction of enzyme APE1 with DNA containing an abasic site, overview
-
additional information
additional information
Michaelis-Menten kinetic study, overview
-
additional information
additional information
-
Michaelis-Menten kinetic study, overview
-
additional information
additional information
pre-steady-state kinetic analysis, kinetic analysis of DNA binding, stopped flow measurements, overview
-
additional information
additional information
-
pre-steady-state kinetic analysis, kinetic analysis of DNA binding, stopped flow measurements, overview
-
additional information
additional information
rate constants of DNA substrate cleavage by APE1 and dissociation constants of APE1/DNA substrate complexes. Analysis of efficacy of APE1 binding to modified DNA duplexes and kinetics of enzyme-substrate complex formation by stopped flow measurements, kinetics, overview
-
additional information
additional information
-
rate constants of DNA substrate cleavage by APE1 and dissociation constants of APE1/DNA substrate complexes. Analysis of efficacy of APE1 binding to modified DNA duplexes and kinetics of enzyme-substrate complex formation by stopped flow measurements, kinetics, overview
-
additional information
additional information
stopped-flow fluorescence techniques to conduct a comparative kinetic analysis of the conformational transitions in human apurinic/apyrimidinic endonuclease 1 (APE1) and in DNA containing an abasic site in the course of their interaction. Influence of different concentrations of Mg2+ and other metal ions on stopped-flow kinetics, overview
-
additional information
additional information
-
stopped-flow fluorescence techniques to conduct a comparative kinetic analysis of the conformational transitions in human apurinic/apyrimidinic endonuclease 1 (APE1) and in DNA containing an abasic site in the course of their interaction. Influence of different concentrations of Mg2+ and other metal ions on stopped-flow kinetics, overview
-
additional information
additional information
-
Steady-state kinetic analysis of Ape1 AP endonuclease activity at 10 mM Mg2+ with and without 5 mM ATP indicates a less than 2fold difference in KM-value but an 19fold enhancement in kcat in the presence of ATP, suggesting an enhancement of the catalytic reaction specifically
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.2
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
pH 7.5, 37°C
-
1
12-mer oligodeoxyribonucleotide containing a tetrahydrofuran analogue at the natural AP site
-
wild-type, pH 7.5, 25°C
-
0.0005
3'-fluorescein-labeled 5'-AACTTCGTGCAGGCATGGTAG(dU)TTGTCTACT-3'
pH 8, 37°C
-
0.0272
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
-
recombinant enzyme
-
10
DNA containing apurinic/apyrimidinic sites
-
5' cleavage of a reduced AP site
-
0.0027
duplex oligonucleotide containing a 5,6-dihydro-2'-deoxyuridine*G pair
-
pH 6.8, 37°C, necleotide incison repair activity
-
0.002
duplex oligonucleotide containing a alpha-2'-deoxyadenosine*T pair
-
pH 6.8, 37°C,nucleotide incison repair activity
-
0.002
duplex oligonucleotide containing a tetrahydrofuran*G pair
-
pH 6.8, 37°C, nucleotide incison repair activity
-
additional information
additional information
-
wild-type APE1 cleaves AP sites more efficiently than D70A mutant with a kcat value for the incision of an AP site aproximately 10fold higher
-
0.000153
12-mer oligodeoxyribonucleotide containing a natural AP site
-
mutant Y171F/P173L/N174K, pH 7.5, 25°C
-
2.8
12-mer oligodeoxyribonucleotide containing a natural AP site
-
wild-type, pH 7.5, 25°C
-
2.91
43-mer oligonucleotide containing the AP-site analog THF at nt 31
-
mutant C99S, presence of 2 mM Mg2+
-
3.36
43-mer oligonucleotide containing the AP-site analog THF at nt 31
-
wild-type, presence of 2 mM Mg2+
-
0.000035
DNA containing 5-OH-C/A
-
+ G 212 mutant, pH 7.5, 37°C, presence of Mg2+
-
0.0000667
DNA containing 5-OH-C/A
-
+ G 212 mutant, pH 7.5, 37°C, presence of EDTA
-
0.000233
DNA containing 5-OH-C/G
-
+ G 212 mutant, pH 7.5, 37°C, presence of Mg2+
-
0.000583
DNA containing 5-OH-C/G
-
P211R mutant, pH 7.5, 37°C, presence of EDTA
-
0.00117
DNA containing 5-OH-C/G
-
+ G 212 mutant, pH 7.5, 37°C, presence of EDTA
-
0.0007
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171A, high salt concentration (150 mM NaCl)
0.0008
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171A, low salt concentration (82 mM NaCl)
0.0009
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171F, low salt concentration (82 mM NaCl)
0.2
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y128A, high salt concentration (150 mM NaCl)
0.3
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y269A, high salt concentration (150 mM NaCl)
0.5
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y128A, low salt concentration (82 mM NaCl)
1.3
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y269A, low salt concentration (82 mM NaCl)
1.6
DNA containing an abasic site
-
pH 7.5, wild-type enzyme, high salt concentration (150 mM NaCl)
10
DNA containing an abasic site
-
pH 7.5, wild-type enzyme, low salt concentration (82 mM NaCl)
1020
THF-containing oligonucleotide
-
APE1 mutant D70A, AP endonuclease activity
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
10000
12-mer oligodeoxyribonucleotide containing a tetrahydrofuran analogue at the natural AP site
-
wild-type, pH 7.5, 25°C
-
64.15
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
-
recombinant enzyme
-
0.63
12-mer oligodeoxyribonucleotide containing a natural AP site
-
mutant Y171F/P173L/N174K, pH 7.5, 25°C
-
30000
12-mer oligodeoxyribonucleotide containing a natural AP site
-
wild-type, pH 7.5, 25°C
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00018
1-methyl-4-[(1E)-1-[2-(6-methyl[1,3]dioxolo[4,5-g]quinolin-8-yl)hydrazinylidene]ethyl]-2-phenyl-1,2-dihydro-3H-pyrazol-3-one
pH not specified in the publication, temperature not specified in the publication
0.00019
8-[(2E)-2-(3-methoxybenzylidene)hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
pH not specified in the publication, temperature not specified in the publication
0.00012
8-[(2E)-2-[(9-ethyl-9H-carbazol-3-yl)methylidene]hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
pH not specified in the publication, temperature not specified in the publication
0.0117
d[(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))3pT]
-
pH 7.6, 37°C
0.0052
d[(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))5pT]
-
pH 7.6, 37°C
0.0023
d[(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))7pT]
-
pH 7.6, 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00028
(2E)-2-(3,4-dihydroxybenzoyl)-3-(3,4-dihydroxyphenyl)prop-2-enenitrile
Homo sapiens
pH and temperature not specified in the publication
0.001
(2E)-2-methyl-3-[3-(methylsulfanyl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl]prop-2-enoic acid
Homo sapiens
pH and temperature not specified in the publication
0.001
(2E)-2-[(3-bromo-1,4-dioxo-1,4-dihydronaphthalen-2-yl)methylidene]-4-methoxybutanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.003
(2E)-2-[(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)methylidene]-4-methoxybutanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0085
(2E)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylidene]-N-methoxydodecanamide
Homo sapiens
pH and temperature not specified in the publication
0.01
(2E)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylidene]dodecanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.003
(2E)-3-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)-2-methylprop-2-enoic acid
Homo sapiens
pH and temperature not specified in the publication
0.003
(2E)-3-(2-chloro-4,5-dimethoxy-3,6-dioxocyclohexa-1,4-dien-1-yl)-2-methylprop-2-enoic acid
Homo sapiens
pH and temperature not specified in the publication
0.002
(2E)-3-(3-bromo-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-2-methylprop-2-enoic acid
Homo sapiens
pH and temperature not specified in the publication
0.001
(2E)-3-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-2-methylprop-2-enoic acid
Homo sapiens
pH and temperature not specified in the publication
0.001
(2E)-3-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-N-(2-hydroxyethyl)-2-methylprop-2-enamide
Homo sapiens
pH and temperature not specified in the publication
0.001
(2E)-3-(3-methoxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-2-methylprop-2-enoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0002
(2E)-3-[3-[dihydroxy(oxido)-lambda5-stibanyl]phenyl]prop-2-enoic acid
Homo sapiens
pH and temperature not specified in the publication
0.002
(2R)-1-(1-benzofuran-2-yl)-2-(1,3-benzothiazol-2-yl)-2-hydroxyethanone
Homo sapiens
pH and temperature not specified in the publication
0.0014
(3-chloro-1-benzothiophen-2-yl)[(2Z)-2-[(2-chlorophenyl)imino]-4-methylidene-3-thia-1-azaspiro[4.5]dec-1-yl]methanone
Homo sapiens
pH and temperature not specified in the publication
0.0018
(3a'S,6a'R)-5'-(1,3-benzodioxol-5-ylmethyl)-3'-(2-carboxyethyl)-7-chloro-2,4',6'-trioxo-1,2,3',3a',4',5',6',6a'-octahydro-2'H-spiro[indole-3,1'-pyrrolo[3,4-c]pyrrol[2]ium]
Homo sapiens
pH and temperature not specified in the publication
0.0028
(5E)-1-(furan-2-ylmethyl)-5-[(2E)-3-(furan-2-yl)prop-2-en-1-ylidene]pyrimidine-2,4,6(1H,3H,5H)-trione
Homo sapiens
pH and temperature not specified in the publication
0.001
(5R)-4-hydroxy-3,5-dimethyl-5-((2S)-3-methylpent-4-en-2-yl)thiophen-2(5H)-one
Homo sapiens
pH and temperature not specified in the publication
0.003
1,3-bis(1,3-benzothiazol-2-ylsulfanyl)propan-2-one
Homo sapiens
pH and temperature not specified in the publication
0.002
1,4-dihydroxy-5,8-bis([2-[(2-hydroxyethyl)amino]ethyl]amino)anthracene-9,10-dione
Homo sapiens
pH and temperature not specified in the publication
0.00025
1-amino-4-[[4-([4-chloro-6-[(4-sulfophenyl)amino]-1,3,5-triazin-2-yl]amino)phenyl]amino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonic acid
Homo sapiens
pH and temperature not specified in the publication
0.0044
1-methyl-4-[(1E)-1-[2-(6-methyl[1,3]dioxolo[4,5-g]quinolin-8-yl)hydrazinylidene]ethyl]-2-phenyl-1,2-dihydro-3H-pyrazol-3-one
Homo sapiens
pH and temperature not specified in the publication
0.00008
1-[[2-(ethylamino)ethyl]amino]-4-(hydroxymethyl)-9H-thioxanthen-9-one
Homo sapiens
pH and temperature not specified in the publication
0.005
1-[[2-(ethylamino)ethyl]amino]-4-methyl-9H-thioxanthen-9-one
Homo sapiens
pH and temperature not specified in the publication
0.016
2,2'-(2-oxo-1H-benzimidazole-1,3(2H)-diyl)diacetic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.011
2,2'-(3,7-dioxo-5,7-dihydro-1H,3H-benzo[1,2-c:4,5-c']difuran-1,5-diyl)diacetic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50 mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.008
2,2'-[(6-oxo-6H-benzo[c]chromene-1,3-diyl)bis(oxy)]dipropanoic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.019
2,2'-[(6-phenylpyrimidine-2,4-diyl)disulfanediyl]diacetic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.0021
2,4,9-trimethylbenzo[b][1,8]naphthyridin-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.0008
2,4-di-tert-butylphenyl 3-chloro-1-benzothiophene-2-carboxylate
Homo sapiens
pH and temperature not specified in the publication
0.00011
2,5-dihydroxy-DL-tyrosine
Homo sapiens
pH and temperature not specified in the publication
0.009
2-((Z)-2-oxo-3-(4-oxo-2-thioxothiazolidin-5-ylidene)indolin-1-yl)acetic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.002
2-(2,4-dichlorophenyl)-6-nitro-4H-3,1-benzoxazin-4-one
Homo sapiens
pH and temperature not specified in the publication
0.0013
2-(4-chlorophenyl)-4-(2'-fluorobiphenyl-4-yl)-5-methyl-1,3-thiazole
Homo sapiens
pH and temperature not specified in the publication
0.008
2-(5-(2-(2-carboxyphenyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl)carbonyl-1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)benzoic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.004
2-(carboxymethyl)-4-([4-[(4-carboxyphenyl)sulfanyl]phenyl]sulfonyl)benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0014
2-aminobenzene-1,3,5-trisulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.019
2-methoxy-3-[(3-methoxybenzyl)carbamoyl]benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.003
2-[(5R)-3-(naphthalen-2-yl)-5-phenyl-2,5-dihydro-1H-pyrazol-1-yl]-2-oxoethyl 5-nitrothiophene-2-carboxylate
Homo sapiens
pH and temperature not specified in the publication
0.003
2-[(5Z)-5-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.0017
2-[(Z)-(4-hydroxy-3-methylphenyl)(3-methyl-4-methylidenecyclohexa-2,5-dien-1-ylidene)methyl]benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.003
2-[5-[1-(carboxymethyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0002
3,3',4,4',5,5'-hexabromobiphenyl
Homo sapiens
pH and temperature not specified in the publication
0.017
3,3'-(1,3,4-thiadiazole-2,5-diyldisulfanediyl)dipropanoic acid
Homo sapiens
small-molecule inhibitor containing 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.015
3,3'-(2-thioxo-1H-benzimidazole-1,3(2H)-diyl)dipropanoic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.000055
3,3'-[(3-carboxy-4-oxocyclohexa-2,5-dien-1-ylidene)methanediyl]bis(6-hydroxybenzoic acid)
Homo sapiens
pH and temperature not specified in the publication
0.00032
3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)-4H-chromen-4-one
Homo sapiens
pH and temperature not specified in the publication
0.0004
3,6,7-trimethoxyphenanthrene-2,5-diol
Homo sapiens
pH and temperature not specified in the publication
0.0004
3,8,9,10-tetrahydroxypyrano[3,2-c]isochromene-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.011
3-((3,4-dimethylphenoxy)methyl)furan-2-carboxylic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.027
3-((pyridin-2-ylthio)methyl)benzofuran-2-carboxylic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.004
3-(1-(carboxymethyl)-5-(4-chlorophenyl)-1H-pyrrol-2-yl)propanoic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.009
3-(1-(carboxymethyl)-5-(4-fluorophenyl)-1H-pyrrol-2-yl)propanoic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.009
3-(1-(carboxymethyl)-5-(thiophen-2-yl)-1H-pyrrol-2-yl)propanoic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.012
3-(1-(carboxymethyl)-5-p-tolyl-1H-pyrrol-2-yl)propanoic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.02
3-(2-carboxyethyl)-4-hydroxyquinoline-6-carboxylic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.006
3-(5-((E)-(3-(carboxymethyl)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl)furan-2-yl)benzoic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.018
3-[(3,4-dichlorobenzyl)carbamoyl]-2-methoxybenzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.018
3-[(3,4-dimethoxybenzyl)carbamoyl]-2-methoxybenzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.016
3-[(3-chlorobenzyl)carbamoyl]-2-methoxybenzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.006
3-[(4Z)-4-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-5-oxo-2-thioxoimidazolidin-1-yl]propanoic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.02
3-[(6-amino-9H-purin-8-yl)sulfanyl]propanoic acid
Homo sapiens
small-molecule inhibitor containing 3 H-bond acceptors and 1 negative ionizable feature, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.004
3-[1-(carboxymethyl)-5-(4-chlorophenyl)-1H-pyrrol-2-yl]propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.015
3-[[4-(carboxymethyl)benzyl]sulfanyl]-8-methyl-5H-[1,2,4]triazino[5,6-b]indole-5-carboxylic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.0017
4'-(2-chloro-6-nitrophenoxy)biphenyl-4-yl 4-tert-butylbenzenesulfonate
Homo sapiens
pH and temperature not specified in the publication
0.006
4-((2-carboxyphenoxy)methyl)-2,5-dimethylfuran-3-carboxylic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.01
4-(4-(4-carboxyphenoxy)phenylsulfonyl)benzene-1,2-dioic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.006
4-(4-(4-carboxyphenylsulfonyl)phenyl)sulfanylbenzene-1,2-dioic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. Then, 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.004
4-(4-(4-carboxyphenylthio)phenylsulfonyl)benzene-1,2-dioic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.02
4-([[(3-carboxy-5-methylfuran-2-yl)methyl]sulfanyl]methyl)-5-methylfuran-2-carboxylic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.0068
4-benzyl-1-(3-[[(3-nitrophenyl)sulfonyl]amino]quinoxalin-2-yl)pyridinium
Homo sapiens
pH and temperature not specified in the publication
0.0068
4-[(4Z)-4-([5-[4-chloro-3-(ethoxycarbonyl)phenyl]furan-2-yl]methylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.012
4-[(4Z)-4-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-5-oxo-2-thioxoimidazolidin-1-yl]butanoic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.000004
4-[dihydroxy(oxido)-lamba5-stibanyl]-2-nitrobenzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0005
4-[methyl(nitroso)amino]benzene-1,2-diol
Homo sapiens
pH and temperature not specified in the publication
0.022
4-[[(2-carboxypropyl)sulfanyl]methyl]-5-methylfuran-2-carboxylic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.005
5,5'-[ethane-1,2-diylbis(sulfanediylmethanediyl)]bis(2-methylfuran-3-carboxylic acid)
Homo sapiens
pH and temperature not specified in the publication
0.005
5,5'-[methanediylbis(sulfanediylmethanediyl)]bis(2-methylfuran-3-carboxylic acid)
Homo sapiens
small-molecule inhibitor containing 4 H-bond acceptors and 3 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.016
5-(((tetrahydrofuran-2-yl)methylthio)methyl)-2-methylfuran-3-carboxylic acid
Homo sapiens
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.00025
5-(acetylamino)-2-[(E)-2-(4-isothiocyanato-3-sulfophenyl)ethenyl]benzenesulfonic acid (non-preferred name)
Homo sapiens
pH and temperature not specified in the publication
0.00025
5-(acetylamino)-2-[2-(4-isothiocyanato-3-sulfophenyl)ethenyl] benzenesulfonic acid
Homo sapiens
pH 8.0, 37°C, recombinant enzyme
0.006
5-([[(4-carboxy-5-methylfuran-2-yl)methyl]sulfanyl]methyl)-3-methylfuran-2-carboxylic acid
Homo sapiens
small-molecule inhibitor containing 4 H-bond acceptors and 3 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.00776
6-amino-4-hydroxy-5-[(4-nitro-2-sulfophenyl)azo]-2-naphtalenesulfonic acid
Homo sapiens
pH 8.0, 37°C, recombinant enzyme
0.00776
6-amino-4-hydroxy-5-[(E)-(4-nitro-2-sulfophenyl)diazenyl]naphthalene-2-sulfonic acid
Homo sapiens
pH and temperature not specified in the publication
0.00885
6-amino-5-[(4-amino-2-sulfophenyl)azo]-4-hydroxy-2-naphtalenesulfonic acid
Homo sapiens
pH 8.0, 37°C, recombinant enzyme
0.00885
6-amino-5-[(E)-(4-amino-2-sulfophenyl)diazenyl]-4-hydroxynaphthalene-2-sulfonic acid
Homo sapiens
pH and temperature not specified in the publication
0.0016
7-chloro-2-(2-fluorophenyl)-4H-3,1-benzoxazin-4-one
Homo sapiens
pH and temperature not specified in the publication
0.0031
7-nitro-1H-indole-2-carboxylic acid
Homo sapiens
pH and temperature not specified in the publication
0.0029
8-[(2E)-2-(1,3-benzodioxol-5-ylmethylidene)hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
Homo sapiens
pH and temperature not specified in the publication
0.0041
8-[(2E)-2-[(9-ethyl-9H-carbazol-3-yl)methylidene]hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
Homo sapiens
pH and temperature not specified in the publication
0.0018
biphenyl-4,4'-diyl bis(3,4-dichlorobenzenesulfonate)
Homo sapiens
pH and temperature not specified in the publication
0.000017
ethyl 4-[4-[dihydroxy(oxido)-lambda5-stibanyl]phenyl]butanoate
Homo sapiens
pH and temperature not specified in the publication
0.0009
N-(3,5-dichlorophenyl)-4-(2'-fluorobiphenyl-4-yl)-5-methyl-1,3-thiazol-2-amine
Homo sapiens
pH and temperature not specified in the publication
0.0016
N-(3-chlorophenyl)-5,6-dihydro-4H-cyclopenta[d][1,2]oxazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.004
N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)-2-(1H-1,2,4-triazol-5-ylsulfanyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0029
N-[3-(1,3-benzothiazol-2-yl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl]acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0033
N-[3-(1,3-benzothiazol-2-yl)-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl]acetamide
Homo sapiens
pH and temperature not specified in the publication
0.002
N-[3-(1,3-benzothiazol-2-yl)-6-(propan-2-yl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl]acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0029
N-[3-(4-phenyl-1,3-thiazol-2-yl)-6-(propan-2-yl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl]acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0003
N-[4-[dihydroxy(oxido)-lambda5-stibanyl]phenyl]benzamide
Homo sapiens
pH and temperature not specified in the publication
0.0071
tetrahydrofuran-2-ylmethyl 6-(furan-2-yl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carboxylate
Homo sapiens
pH and temperature not specified in the publication
0.011
[(3Z)-3-(3-[[(2-hydroxyphenyl)carbonyl]amino]-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)-2-oxo-2,3-dihydro-1H-indol-1-yl]acetic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.006
[(3Z)-3-[3-(4-bromophenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]-2-oxo-2,3-dihydro-1H-indol-1-yl]acetic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.013
[(5Z)-5-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Homo sapiens
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.0017
[4-(2,5-dimethyl-1H-pyrrol-1-yl)phenoxy]acetic acid
Homo sapiens
pH and temperature not specified in the publication
0.0016
N-(3-chlorophenyl)-5,6-dihydro-4H-cyclopenta[d]isoxazole-3-carboxamide
Homo sapiens
-
-
0.004
2,2'-[butane-1,4-diylbis(1H-benzimidazole-2,1-diyl)]diacetic acid
Homo sapiens
small-molecule inhibitor containing 4 H-bond acceptors and 3 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30°C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.004
2,2'-[butane-1,4-diylbis(1H-benzimidazole-2,1-diyl)]diacetic acid
Homo sapiens
pH and temperature not specified in the publication
additional information
additional information
Homo sapiens
The APE1 inhibitory profile of some of the most potent compounds indicates that along with two terminal fingerprint negatively ionizable features or bioisostere groups of negatively ionizable features, an optimum sized central hydrophobic core with or without a favorably substituted H-bond acceptor-donor functional group is essential for a compound being recognized by APE1 and inhibit its catalytic activity
-
additional information
additional information
Homo sapiens
-
The APE1 inhibitory profile of some of the most potent compounds indicates that along with two terminal fingerprint negatively ionizable features or bioisostere groups of negatively ionizable features, an optimum sized central hydrophobic core with or without a favorably substituted H-bond acceptor-donor functional group is essential for a compound being recognized by APE1 and inhibit its catalytic activity
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
The necessity of APE1 for cellular survival and its frequent overexpression in tumor cells strongly suggest a fundamental role of this protein in preventing cell death and in controlling cellular proliferation.
additional information
The regulatory functions of the different APE1 activities can be fine-tuned and implemented via three different mechanisms: increase in APE1 level after transcriptional activation, relocalization of APE1 from the cytoplasm to the nucleus, and modulation of the posttranslational modifications of APE1, such as acetylation and phosphorylation.
additional information
-
10 mM Mg2+, all Cys mutants except those with C99S mutation are at least as active as the wild-type APE1
additional information
-
750 nM substrate and 100 nM enzyme and a reaction time of 3 h is sufficient to convert most, if not all, of the Rp stereoisomer substrate DNA into product
additional information
-
activity of Cys99 mutants is comparable to that of the wild-type in 0.5 or 2mM Mg2+, while only the Cys99 mutants are strongly inhibited at 5 mM and higher Mg2+ concentration
additional information
-
APE-1 expression in tissues from Helicobacter pylori-infected subjects is significantly increased compared to that in tissues from subjects after successful eradication therapy
additional information
-
APE/Ref-1 accounts for 95% of the total apurinic/apyrimidinic endonuclease activity and is essential for the protection of cells against the toxic effects of several classes of DNA-damaging agents
additional information
-
APE/Ref-1 is involved in the regulation of metastatic potential in melanoma cells
additional information
-
APE/Ref-1 is very sensitive to redox-status alterations. ROS regulates its activity and expression on both transcriptional and posttranscriptional levels
additional information
-
Ape1 has only slightly more robust activity on the partial DNA-DNA duplex than on the comparable DNA/RNA duplex.
additional information
-
Ape1/Ref-1 increases the expression of glial cell-derived neurotropic factor receptor alpha1 (GFRalpha1), a key receptor for glial cell-derived neurotropic factor (GDNF). Expression of Ape1/Ref- 1 leads to an increase in the GDNF responsiveness in human fibroblast. Ape1/Ref-1 induced GFRalpha1 transcription through enhances binding of NF-kappaB complexes to the GFRalpha1 promoter.
additional information
-
By adding of purified Y-box-binding protein-1 to the nuclease reaction containing 0.2 microg of TAP-hNTH1 (minimum of protein required to see cleavage of the DNA duplex), there is an 12fold increase in cleavage activity
additional information
-
Cell-based analysis of redox activity for hApe1 Cys-mutants using an in vitro EMSA redox assay in which reduction of the trancription factor AP-1 by hApe1 results in a shifted band. Only C65A hApe1 is found to be redox inactive.
additional information
-
creation of three-strand substrates provided a 2- to 2.5fold increase in the specific activity of Ape1 over the partial duplex with the abasic lesion positioned at the ssDNA-dsDNA junction (54Fendbubble18-18DNA)
additional information
-
Cys99 in hAPE1 as a critical residue modulating function for ensuring optimum activity
additional information
-
decreased levels of AP endonuclease activity (smaller amount of cleaved 14-mer products and greater amount of uncleaved 26-mer oligonucleotides) are observed in both H460 and H69 cells that express high levels of endogenous Bcl2 as compared with the other cell lines that express undetectable levels of Bcl2
additional information
-
expression of endogenous Bcl2 is associated with decreased APE1 endonuclease activity in various human lung cancer cells
additional information
-
GFRalpha1 levels correlates proportionally with Ape1/Ref-1 in cancer cells
additional information
-
in neuronal cells, the Ape1/Ref-1-mediated increase in GDNF responsiveness not only stimulated neurite outgrowth but also protected the cells from beta-amyloid peptide and oxidative stress
additional information
-
Increased expression of APE/Ref-1 protein in nucleus of different human melanoma cell lines
additional information
-
involvement of APE/Ref-1 in the process of inflammation
additional information
-
no activity is detected using a probe without 8-oxoguanine residue demonstrating the specificity of hNTH1 for oxidized DNA duplex
additional information
-
substrates with either a purine (G) or a pyrimidine (C) positioned opposite the AP site and two purines flanking the abasic site shows that Ape1 incision activity under optimal reaction conditions is two to threefold higher with the GFT-CCA, CFA-GCT, and CFT-GGA arrangements relative to GFA-CCT
additional information
-
TAP-hNTH1 expressing cells transfected with a small interference RNA specific to hNTH1 show decreased protein levels and nuclease activities toward the radioactive duplex 8-oxoguanine
additional information
-
the enzyme is responsible for eliminating as many as 105 potentially mutagenic and genotoxic lesions from the genome of each cell every day
additional information
-
the knockdown of endogenous Ape1/Ref-1 in pancreatic cancer cells markedly suppresses GFRalpha1 expression and invasion in response to GNDF, while overexpression of GFRalpha1 restores invasion
additional information
-
the MCF7-eluted TAP-hNTH1 protein exhibits nuclease activities on a radioactive duplex containing 8-oxoguanine residues
additional information
-
The nucleotide incision repair (NIR) activity of APE1 provides an alternative and complementary repair pathway to BER
additional information
-
The specific activity is significantly increased in the case of the D70A mutant enzyme. Upon incubation at 37°C, 5 nM of purified APE1 mutant D70A remove most of the 3'-phosphoglycolate residues in 10 min, while the same enzyme amounts of APE1 converts only around 60% and 50% of the substrate into the corresponding 3'-OH form.
additional information
-
Y-box-binding protein-1 binds specifically to the auto-inhibitory domain of hNTH1 to stimulating its activity
additional information
-
Y-box-binding protein-1 strongly stimulates in vitro the activity of hNTH1 toward DNA duplex probes containing oxidized bases, lesions prone to be present in cisplatin treated cells
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
7.5 - 8
7.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
37
37
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
APE1 is highly expressed in selected regions of the central nervous system
increased nuclear expression of APE1 in neuronal and glial cells in both familial and sporadic Alzheimer
a reduction in APE1 expression, followed by an increase in the apoptotic rate, occurs in the hippocampus after a hypoxic-ischemic injury, patients with Alzheimer show an increased expression of APE1 levels in senile plaques and plaque-like structures
-
human umbilical vein endothelial cells are infected with adenovirus encoding APE/Ref-1
-
APE-1 expression is mainly localized in epithelial cells within gastric adenoma
-
various cell lines, Bcl2, a major antiapoptotic and/or oncogenic protein, is found to co-express with APE1 in H69 and H460 but not in other tested lung cancer cells
-
Helicobacter pylori (CagA+) water-extract protein (HPWEP)-stimulated
-
APE1 protein is elevated in 72% of the tissues and among those with a known clinical outcome. There is a significant correlation between high APE1 expression levels and reduced survival times
-
nuclear expression of APE1 in epidermal layers is markedly up-regulated in psoriatic skin, APE1 is essential for the transcriptional activation and nuclear translocation of hypoxia-inducible factor-1alpha and NF-kappaB
additional information
additional information
APE1 is synthesized in human cells in large quantities
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
AcAPE1 is exclusively associated with chromatin throughout the cell cycle and remains bound to the condensed chromosomes. Immunohistochemic detection, the AcAPE1 Ab is highly specific for recognizing APE1 species acetylated at the N-terminal Lys6 residue and does not cross-react with a 50fold excess of unmodified APE1. Colocalization of AcAPE1 with histone H3 or active enhancer-specific histone marker acetylated H3K27 (H3K27Ac). Positive charges of acetylable Lys residues but not their acetylation are essential for the chromatin binding of APE1
APE1 is located in the area of an AP site on the strand containing the AP site relative to the DNA helix, bending the helix in the process. APE1 is fixed on the DNA through two enzyme sites. One of them containing the Met270 and Met271 residues interacts with the minor groove, and another containing Arg177,with the major DNA groove. The Arg177 residue forms a hydrogen bond with the 3'-phosphate of the AP site. APE1 stabilizes the out-of-helix position of the AP site and is efficiently anchored on the DNA. Interaction of Arg177 with DNA slows dissociation of APE1 from the product of the endonuclease reaction
cytoplasmic localization of APE1in fibroblasts, spermatocytes, thyrocytes, lymphocytes, hepatocytes, and hippocampal cells is associated with high metabolic or proliferative rates and may be related to a cell cycle-dependent expression
APE1 protein is also localized within mitochondria in different cell types, mitochondrial localization of APE1 is associated to a potential role in DNA repair of oxidized bases in the mitochondrial genome
APE1 subcellular distribution, in different mammalian cell types, is mainly nuclear and is critical in controlling cellular proliferative rate
-
translocation of the cytoplasmic enzyme into the nucleus occurs during DNA damage
-
the enzyme preferentially resides in the nucleus with conditional distribution in the mitochondria
-
-
-
the first 7 residues and residues 8-13 can independently promote nuclear import
-
When THP-1 cells are incubated with high-mobility group box 1 for 12 h, cytoplasmic APE1 proteins are substantially translocated into nucleus. APE1 proteins are significantly translocated from cytoplasmic to nuclear fractions in THP-1 cells at 24 h after high-mobility group box 1 stimulation. Overexpression of APE1 in human primary monocytes with adenoviral transduction leads to abundant protein expression in the cytoplasmic and nuclear fractions.
additional information
expression and subcellular localization are altered in several metabolic and proliferative disorders such as in tumors and aging
-
additional information
depending on the type of cells, APE1 is localized primarily in the nucleus, cytoplasm, or mitochondria
-
additional information
-
depending on the type of cells, APE1 is localized primarily in the nucleus, cytoplasm, or mitochondria
-
additional information
-
high-mobility group box 1 stimulation induces the nuclear translocation of APE1 protein, and siRNA transfection and adenoviral transduction results in differential expression and localization patterns in activated macrophages
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
basic human AP endonuclease is a multifunctional protein. AP endonucleases fall into two families depending on the similarity of their amino acid sequence with exonuclease III (ExoIII or Xth) or endonuclease IV (EndoIV or Nfo) from Escherichia coli. APE1 belongs to the large nuclease family related to ExoIII from Escherichia coli. Enzymes of the ExoIII family including APE1 exhibit several enzymatic activities manifested more or less effectively: AP endonuclease, 3'-phosphodiesterase, 3'-phosphatase, and 3'-5'-exonuclease
malfunction
metabolism
mechanisms of AP site cleavage by enzymes from the base excision repair system (BER), overview. Enzyme Polbeta in combination with APE1 is able to perform synthesis with strand displacement and simultaneously correction of Polbeta errors with catalysis by 3'-5'-exonuclease activity of the APE1. A Schiff base is formed as an intermediate in the reactions catalyzed by AP lyases and 5'-dRP lyases. One of the repair proteins interacting with the AP sites via formation of a Schiff base is poly(ADP-ribose)polymerase 1 (PARP1). PARP1 is known as a sensor of single-stranded breaks and as a protein regulator of BER. If exogenous APE1 is added prior to irradiation, the efficiency of the PARP1 and FEN1 labeling decreases (but not of the Polbeta), these proteins compete for binding to this DNA substrate. Interaction between various enzymes and proteins participating in BER, overview
physiological function
malfunction
metabolism
a nucleophilic residue of ALKBH1 reacts with the electrophilic C3' of the alpha,beta-unsaturated aldehyde of the 5'-product. The addition of a competing nucleophile, specifically 2-mercaptoethanol, reduces the extent of adduct formation
physiological function
additional information
malfunction
APE1 lacking the first 34 amino acids at the Nterminus, unlike wild-type enzyme, is unable to form cross-links with BS-AP DNAs that testifies to the involvement of disordered N-terminal extension, which is enriched in lysine residues, in the interaction with AP sites.
malfunction
protein acetylation is an important protein modification in living cells and has an impact on pathological conditions. A profound deregulation of APE1/Ref-1 acetylation (on Lys35) status in triple negative breast cancer is revealed
malfunction
the expression of transforming growth factor beta (TGFbeta) is significantly reduced in APE1-deficient osteosarcoma cells. Transforming growth factor beta promotes cancer metastasis through various mechanisms including immunosuppression, angiogenesis, and invasion. APE1, TGFbeta, and microvessel density (MVD) have a pairwise correlation in osteosarcoma tissue samples, whereas TGFbeta, tumor size, and MVD are inversely related to the prognosis of the cohort. High expression of APE1, TGFbeta, and microvessel density (MVD) correlate with poor prognosis of osteosarcoma patients. Apurinic/apyrimidinic endonuclease 1-siRNA-mediated downregulation in osteosarcoma cells inhibits expression of TGFbeta1. Apurinic/apyrimidinic endonuclease 1-siRNA inhibits the capability to enhance HUVEC migration and tube formation of tumor cells through the TGFbeta/Smad3 signaling pathway. Tumor angiogenesis and growth in xenografts are suppressed by APE1-siRNA
malfunction
the redox-deficient truncated APE1 protein lacking the first N-terminal 61 amino acid residues (APE1-N?61) cannot stimulate DNA glycosylase activities of OGG1, MBD4, and ANPG on duplex DNA substrates
physiological function
isoform Ape1 is an essential factor stabilizing telomeric DNA, and its deficiency is associated with telomere dysfunction and segregation defects in immortalized cells maintaining telomeres by either the alternative lengthening of telomeres pathway or telomerase expression or in normal human fibroblasts
physiological function
AP endonuclease 1 (APE1) is a multifunctional protein abundant in human cells that is essential in maintaining multiple cellular functions. AP endonuclease 1 (APE1) takes part in the base excision repair (BER). It prevents trinucleotide repeat (TNR) expansions via its 3'-5'-exonuclease activity and stimulatory effect on DNA ligation during BER in a hairpin loop. Coordinating with flap endonuclease 1, the APE1 3'-5'-exonuclease activity cleaves the annealed upstream 3'-flap of a double-flap intermediate resulting from 5'-incision of an abasic site in the hairpin loop. Furthermore, APE1 stimulates DNA ligase I to resolve a long double-flap intermediate, thereby promoting hairpin removal and preventing TNR expansions
physiological function
APE1 is one of the key enzymes taking part in the repair of damage to DNA. The primary role of APE1 is the initiation of the repair of AP-sites by catalyzing the hydrolytic incision of the phosphodiester bond immediately 5' to the damage. In addition to the AP-endonuclease activity, APE1 possesses 3'-5'-exonuclease activity, which presumably is responsible for cleaning up nonconventional 3'-ends that were generated as a result of DNA damage or as transition intermediates in DNA repair pathways
physiological function
APE1 is unable to cleave apurinic/apyrimidinic (AP) sites in spite of formation of the Schiff-base-dependent intermediate, which is prerequisite for the beta-elimination mechanism. Clustered AP sites are more cytotoxic than isolated AP lesions because double strand breaks (DSB) can be formed during repair of closely positioned bistranded AP sites. Formation of DSB due to simultaneous cleavage of bistranded AP sites may be regulated by proteins specifically interacting with this complex lesion
physiological function
Apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in the genome, inhibit transcription and block replication. The primary enzyme that repairs AP sites in mammalian cells is the AP endonuclease (APE1), which functions through the base excision repair (BER) pathway. Human DNA repair enzyme APE1 is a ubiquitous and multifunctional protein. It plays a central role in the repair of spontaneously generated AP sites and oxidative and alkylated DNA damage in the genome via the BER pathwayMammalian cells, unlike Saccharomyces cerevisiae or Escherichia coli cells, require acetylation of APE1 for the efficient repair of AP sites and base damage in the genome. APE1 acetylation is an integral part of the BER pathway for maintaining genomic integrity. Apart from its DNA repair function, APE1 functions as a redox activator of many transcription factors, as well as a direct transcriptional coregulator of many genes. APE1 is essential for embryonic development and for cell viability and/or proliferation in cultures. Human APE1 is unique in that it has an N-terminal disordered 42 amino acids and has both DNA repair and transcriptional regulatory activities. AcAPE1 is exclusively associated with chromatin throughout the cell cycle. Acetylation of APE1 enhances its AP catalytic efficiency, and APE1 acetylation enhances its interaction with downstream BER proteins and stability on chromatin. APE1 acetylation plays a role in cell survival and/or proliferation in response to genotoxic stress
physiological function
apurinic/apyrimidinic endonuclease 1 (Ape1) is an important enzyme in the base excision repair mechanism, responsible for the backbone cleavage of abasic DNA through a phosphate hydrolysis reaction
physiological function
apurinic/apyrimidinic endonuclease 1 is a multifunctional protein playing crucial roles in DNA base excision repair and redox regulation of gene expression, activities that are functionally and structurally independent of each other. The APE1 redox activity stimulates numerous transcriptional factors, including activator protein-1 (AP-1), nuclear factor-kappaB (NF-happaB), and HIF-1. These factors are involved in mediating VEGF gene expression; HIF-1 and NF-kappaB, in particular, increased VEGF expression in response to hypoxia. Apurinic/apyrimidinic endonuclease 1 (APE1) is a dually functional protein possessing both base excision repair and redox activities, it is involved in tumor angiogenesis. APE1, TGFbeta, and microvessel density (MVD) have a pairwise correlation in osteosarcoma tissue samples, whereas TGFbeta, tumor size, and MVD are inversely related to the prognosis of the cohort. High expression of APE1, TGFbeta, and microvessel density (MVD) correlate with poor prognosis of osteosarcoma patients. APE1 may indirectly regulate angiogenesis through a TGFbeta-dependent pathway
physiological function
apurinic/apyrimidinic sites (AP sites) are among the most abundant DNA damages. They can emerge because of spontaneous hydrolysis of the N-glycoside bond and during removal of the damaged DNA bases by DNA glycosylases. In mammalian cells up to 10000 AP sites emerge daily primarily due to apurinization of DNA. The number of such damages increases dramatically during intensive oxidative stress, X-ray and UV irradiation, and other actions. The deoxyribose residues in the AP sites exist in different forms that are in equilibrium. The acyclic aldehyde form of an AP site can form a Schiff base with amino groups in proteins, most often with the epsilon-NH2 group of lysine residues. AP endonucleases are the most important enzymes involved in the DNA repair that initiates the repair of AP sites. Human apurinic/apyrimidinic endonuclease 1 (APE1) is one of the key participants in the DNA base excision repair system. The major contribution to AP site cleavage in mammalian cells is provided by APE1 (over 95% of damages). APE1 hydrolyzes DNA adjacent to the 5'-end of an AP site to produce a nick with a 3'-hydroxyl group and a 5'-deoxyribose phosphate moiety. APE1 exhibits 3'-phosphodiesterase, 3'-5'-exonuclease, and 3'-phosphatase activities. APE1 is also identified as a redox factor (Ref-1). Role of APE1 in the DNA repair process and in other metabolic processes, overview. The APE1 protein is required for viability of human cell culture. APE1 is required not only for hydrolysis of AP sites generated by monofunctional DNA glycosylases, but also for processing of the products of bifunctional DNA glycosylases catalyzing beta-elimination. The enzyme is obviously involved in the cell response system to the action of some genotoxic agents. Participation of APE1 in stimulation of the DNA glycosylase, lyase, polymerase, flap endonuclease, and DNA ligase activities of BER enzymes likely reflects the role of this enzyme in coordination of different stages of DNA repair to achieve its optimal efficiency
physiological function
human apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional protein which is essential in the base excision repair (BER) pathway of DNA lesions caused by oxidation and alkylation. This protein hydrolyzes DNA adjacent to the 5'-end of an apurinic/apyrimidinic (AP) site to produce a nick with a 3'-hydroxyl group and a 5'-deoxyribose phosphate moiety or activates the DNA binding activity of certain transcription factors through its redox function. Role for APE1/Ref-1 in the pathogenesis of cancer and in resistance to DNA-interactive drugs. APE1/Ref-1 plays a vital role in mammalian cells with implication in human pathologies. DNA damage and chronic oxidative stress are involved in various neurodegenerative disorders, including Alzheimer's, Parkinson's, Huntington's diseases, and amyotrophic lateral sclerosis. APE1/Ref-1 signaling pathway in hepatocellular carcinoma stimulates cellular proliferation, enhances anti-apoptosis, and facilitates metastasis
physiological function
human apurinic/apyrimidinic endonuclease APE1 is one of the key enzymes of the base excision DNA repair system. The main biological function of APE1 is the hydrolysis of the phosphodiester bond on the 5'-side of an apurinic/apyrimidinic site (AP-site) to give the 5'-phosphate and 3'-hydroxyl group. The level of enzymatic activity of human AP-endonuclease APE1 has a considerable influence on the process of the removal of DNA lesions. APE1 is an extremely active enzyme which is able to process many synthetic analogues of the AP-site such as tetrahydrofuran (F-site) or alpha,omega-alkane diols
physiological function
most of the biological importance of APE1 in the DNA repair pathways is associated with the high affinity for the abasic nucleotide and nicking of DNA hydrolytically 5' to the AP-site. APE1 has the ability to incise the DNA sugar-phosphate backbone 5' to structurally unrelated lesions such as alpha-anomeric 2'-deoxynucleosides, various red/ox-modified pyrimidines and etheno-adducts
physiological function
the base excision repair (BER) pathway consists of sequential action of DNA glycosylase and apurinic/apyrimidinic (AP) endonuclease necessary to remove a damaged base and generate a single-strand break in duplex DNA. Human multifunctional AP endonuclease 1 (APE1) plays essential roles in BER by acting downstream of DNA glycosylases to incise a DNA duplex at AP sites and remove 3'-blocking sugar moieties at DNA strand breaks. Human apurinic/apyrimidinic (AP) endonuclease, APE1, stimulates DNA glycosylases, e.g. human 8-oxoguanine-DNA glycosylase (OGG1), by increasing their turnover rate on duplex DNA substrates, overview. The redox domain of APE1 is necessary for the active mode of stimulation of DNA glycosylases (e.g. of uracil-DNA glycosylase activity of MBD4). Consequently, APE1 shows DNA length dependence with preferential repair of short DNA duplexes. APE1-catalyzed oligomerization along DNA induces helix distortions, which in turn enable conformational selection and stimulation of DNA glycosylases
malfunction
-
knocking down Ape1/Ref-1 expression enhances estrogen responsiveness of the progesterone receptor and pS2 genes but does not alter the expression of the constitutively active 36B4 gene
malfunction
-
short hairpin RNA-mediated stable suppression of APE-1 results in increased apoptosis in gastric epithelial cells after Helicobacter pylori infection
malfunction
-
siRNA knockdown of endogenous APE1 impairs high-mobility group box 1-mediated cytokine expression and MAPK activation in THP-1 cells
physiological function
-
APE1 functions as a critical rate-limiting enzyme in DNA base excision repair and accounts for nearly all of the AP site incision activities in cell extracts, APE1 also exerts unique redox activity to regulate the DNA-binding affinity of certain transcriptional factors by controlling the redox status of their DNA-binding domain
physiological function
-
APE1 has a central role in the coordination of base excision repair
physiological function
-
APE1 is a dual regulator of inflammatory signaling to high-mobility group box 1 by human monocytes/macrophages. Forced cytoplasmic overexpression of APE1 profoundly attenuates the upregulation of high-mobility group box 1-mediated reactive oxygen species generation, cytokine secretion, and cyclooxygenase-2 expression by primary monocytes and macrophage-like THP-1 cell lines, the extracellular release of high-mobility group box 1 by activated macrophages is inhibited by APE1 transfection
physiological function
-
APE1 is a key multifunctional protein involved in DNA base excision repair
physiological function
-
APE1 is a key upstream regulator in TLR2-dependent keratinocyte inflammatory responses
physiological function
-
APE1 is a multifunctional enzyme that plays a central role in base excision repair of DNA and is also involved in the alternative nucleotide incision repair pathway
physiological function
-
APE1 is the major nuclease for excising abasic sites and particular 3'-obstructive termini from DNA, and is an integral participant in the base excision repair pathway
physiological function
-
APE1 regulates c-myc mRNA level possibly via its endoribonuclease activity
physiological function
-
APE1 stimulates the multiple-turnover excision of hypoxanthine by alkyladenine DNA glycosylase but has no effect on single-turnover excision
physiological function
-
Ape1/Ref-1 enhances the interaction of estrogen receptor alpha with estrogen-response elements in DNA, Ape1/Ref-1 alters expression of the endogenous, estrogen-responsive progesterone receptor and pS2 genes in MCF-7 cells and associates with estrogen-response elements-containing regions of these genes in native chromatin
physiological function
-
both DNA repair and acetylation functions of APE-1 modulate programmed cell death, the DNA repair activity of APE-1 inhibits the mitochondrial pathway, whereas the acetylation function inhibits the extrinsic pathway during Helicobacter pylori infection
physiological function
-
in addition to the apurinic/apyrimidinic DNA endonuclease activity, APE1 has 3'-5' DNA exonuclease, 3'-phosphodiesterase, and RNase H activities
physiological function
-
nuclear factor -kappaB is activated by cytoplasmic, but not nuclear, Ape1 to cause Cox-2 expression. Ape1 can enhance lung tumor malignancy through nuckear factor-kappaB activation
physiological function
human enzyme APE2 performs most of the essential functional residues of the exonuclease III-like proteins. APE2 has 518 amino acids. Unlike APE1/Ref-1, APE2 shows only weak capacity to exhibit AP site repair activity. APE2 has no the N-terminal tail that is present in APE1/Ref-1 and as such does not possess redox activity
physiological function
the 6-methyl adenine demethylase activity is very low. The demethylase activity is less than half that of the apurinic/apyrimidinic lyase activity when ALKBH1 samples are assayed using identical buffer conditions. The two enzymatic activities are located in distinct but partially overlapping active sites for the two reactions
additional information
a set of AP DNA duplexes containing AP sites in both strands in different mutual orientation (BS-AP DNAs) is used for search in the extracts of human cells proteins specifically recognizing clustered AP sites
additional information
-
a set of AP DNA duplexes containing AP sites in both strands in different mutual orientation (BS-AP DNAs) is used for search in the extracts of human cells proteins specifically recognizing clustered AP sites
additional information
association of APE1 with undamaged DNA reduces effective concentration of the enzyme and subsequently decreases APE1-catalyzed cleavage rates on long DNA substrates. APE1 oligomers on DNA induce helix distortions thereby enhancing molecular recognition of DNA lesions by DNA glycosylases via a conformational proofreading/selection mechanism. Thus, APE1-mediated structural deformations of the DNA helix stabilize the enzyme-substrate complex and promote dissociation of human DNA glycosylases from the AP site with a subsequent increase in their turnover rate. APE1 shows DNA length dependence with preferential repair of short DNA duplexes. Electron microscopic analysis of DNA complexes with the APE1 protein
additional information
-
association of APE1 with undamaged DNA reduces effective concentration of the enzyme and subsequently decreases APE1-catalyzed cleavage rates on long DNA substrates. APE1 oligomers on DNA induce helix distortions thereby enhancing molecular recognition of DNA lesions by DNA glycosylases via a conformational proofreading/selection mechanism. Thus, APE1-mediated structural deformations of the DNA helix stabilize the enzyme-substrate complex and promote dissociation of human DNA glycosylases from the AP site with a subsequent increase in their turnover rate. APE1 shows DNA length dependence with preferential repair of short DNA duplexes. Electron microscopic analysis of DNA complexes with the APE1 protein
additional information
molecular dynamics simulations of Ape1 complexed to its substrate DNA performed for models containing 1 or 2 Mg21-ions as cofactor located at different positions show a complex with 1 metal ion bound on the leaving group site of the scissile phosphate to be the most likely reaction-competent conformation. Active-site residue His309 is found to be protonated based on pKa calculations and the higher conformational stability of the Ape1-DNA substrate complex compared to scenarios with neutral His309. Simulations of the D210N mutant further support the prevalence of protonated His309 and strongly suggest Asp210 as the general base for proton acceptance by a nucleophilic water molecule. Enzyme modelling based on the crystal structure of the phosphorothioate substrate complex with Mn2+ as metal cofactor (PDB ID 5DG0). Residue His309 is essential for substrate binding and the phosphate hydrolysis step. In terms of substrate binding, Tyr171 has the possibility to form a hydrogen bond with the non-bridging oxygen atom of the AP-site
additional information
stopped-flow fluorescence techniques are used to conduct a comparative kinetic analysis of the conformational transitions in human apurinic/apyrimidinic endonuclease 1 (APE1) and in DNA containing an abasic site in the course of their interaction. Analysis of enzyme-substrate complexes with bound Mg2+
additional information
-
stopped-flow fluorescence techniques are used to conduct a comparative kinetic analysis of the conformational transitions in human apurinic/apyrimidinic endonuclease 1 (APE1) and in DNA containing an abasic site in the course of their interaction. Analysis of enzyme-substrate complexes with bound Mg2+
additional information
substrate specificity and substrate binding, molecular dynamics simulations. Molecular modelling of the APE1 complex with 13 ntDNA duplexes containing 1,N6-ethenoadenosine, alpha-adenosine, 5,6-dihydrouridine or F-site. Model structures of APE1-DNA complexes show that the pocket of the active site is formed by amino acid residues Asn174, Asn212, Asn229, Ala230, Phe266 and Trp280
additional information
-
substrate specificity and substrate binding, molecular dynamics simulations. Molecular modelling of the APE1 complex with 13 ntDNA duplexes containing 1,N6-ethenoadenosine, alpha-adenosine, 5,6-dihydrouridine or F-site. Model structures of APE1-DNA complexes show that the pocket of the active site is formed by amino acid residues Asn174, Asn212, Asn229, Ala230, Phe266 and Trp280
additional information
the N-terminal domain (about 6 kDa, 60 amino acids) is responsible for the redox function of APE1, which is independent of the repair functions of this enzyme, and it contains the nuclear export signal. The second human AP endonuclease (APE2) also belongs to the ExoIII family, but the level of its endonuclease activity is significantly lower than of APE1. Amino acids such as Asp219, Asp90, and Asp308 are functionally important, D219 in APE1 plays a key function in repair. Tyr171 does not interact directly with the AP site, but participates in the catalysis of the APE1 endonuclease reaction in the form of a phenolate ion, i.e. it attacks phosphate at the 5'-side of the AP site
additional information
-
the N-terminal domain (about 6 kDa, 60 amino acids) is responsible for the redox function of APE1, which is independent of the repair functions of this enzyme, and it contains the nuclear export signal. The second human AP endonuclease (APE2) also belongs to the ExoIII family, but the level of its endonuclease activity is significantly lower than of APE1. Amino acids such as Asp219, Asp90, and Asp308 are functionally important, D219 in APE1 plays a key function in repair. Tyr171 does not interact directly with the AP site, but participates in the catalysis of the APE1 endonuclease reaction in the form of a phenolate ion, i.e. it attacks phosphate at the 5'-side of the AP site
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37000
35000
36000
37000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
additional information
These two biological activities are located in two functionally distinct domains. The n-terminus, containing the nuclear localization signal region, is principally devoted to the redox activity, through Cys65, while the c-terminus exerts the enzymatic activity on the abasic sites of DNA.
additional information
analysis of enzyme-substrate complexes with bound Mg2+
additional information
the N-terminal domain (about 6 kDa, 60 amino acids) is responsible for the redox function of APE1, which is independent of the repair functions of this enzyme, and it contains the nuclear export signal
additional information
-
the N-terminal domain (about 6 kDa, 60 amino acids) is responsible for the redox function of APE1, which is independent of the repair functions of this enzyme, and it contains the nuclear export signal
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
acetylation
phosphoprotein
several different phosphorylation sites are scattered throughout the molecule, these potential phosphorylation sites include consensus sequences for casein kinase I and II, for protein kinase C, and for glycogen synthase kinase 3
proteolytic modification
S-nitrosation
2 of the 7 Cys residues (Cys93 and Cys310) of APE1 undergoes S-nitrosation in response to nitric oxide stimulation, leading to nucleus to cytoplasm relocalization of the protein in a CRM1-independent process, possibly as a consequence of demasking a putative nuclear export signal
sumoylation
acetylation
-
necessary for the repression of parathyroid hormone secretion by APE1/Ref-1
phosphoprotein
-
phosphorylation of APE1/Ref-1 by several different kinases has been shown to affect both its DNA repair and reducing properties
additional information
acetylation
mammalian cells, unlike Saccharomyces cerevisiae or Escherichia coli cells, require acetylation of enzyme APE1 for the efficient repair of AP sites and base damage in the genome. APE1 acetylation is an integral part of the BER pathway for maintaining genomic integrity. AcAPE1 is acetylated at Lys6 and Lys7 residues in the N-terminal domain, and acetylation modulates the transcriptional coregulatory activity of enzyme APE1. APE1 is acetylated after binding to AP site damage in the chromatin, chromatin association is necessary for APE1 to be acetylated.Acetylation of APE1 enhances its AP endonuclease activity or catalytic efficiency. Methoxyamine treatment completely abrogates APE1 acetylation in a dose- and time-dependent manner. Acetylation induces a conformational change in APE1
proteolytic modification
Proteolysis occurring at residue Lys31, this post-translational regulation of APE1 protein is responsible for enhanced cell death mediated by granzyme A and granzyme K. Truncated APE1 looses its AP-endonuclease activity and acquire a nonspecific DNAse function.
sumoylation
high probability, putative sumoylation site, which contains a canonical sumoylation K-X-D/E motif, addition of a small ubiquitin-like modifier (SUMO) molecule to the target protein accounts for an increase of 12 kDa of the apparent molecular mass of the target protein. The effects of posttranslational modification by SUMO to compete for target lysines enhance or inhibit interactions with other proteins (or other binding partners such as DNA) or induce conformational changes.
additional information
APE1 is subjected to different types of posttranslational modifications: acetylation at several residues in the N-domain, nitrosylation on residues of the C-domain, ubiquitination, proteolysis, and sumoylation
additional information
-
APE1 is subjected to different types of posttranslational modifications: acetylation at several residues in the N-domain, nitrosylation on residues of the C-domain, ubiquitination, proteolysis, and sumoylation
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
to 1.92 A resolution with a single Mg2+ ion in the active site. The structure reveals ideal octahedral coordination of Mg2+ via two carboxylate groups and four water molecules. One residue that coordinates Mg2+ directly and two that bind inner-sphere water molecules are strictly conserved in the DNase I superfamily
X-ray diffraction analysis of APE1 complexes with oligomeric DNA-duplexes (11 or 15 bp) containing an AP site. There is only one bivalent metal ion in the APE1 active site present in the crystal formed at pH 4.6. In the structure produced at pH 7.5, i.e. under conditions optimal for endonuclease activity, two metal ions are located in the active site of the enzyme
mutant C65A hApe1 protein is diluted to 10 mg/ml in 10 mM HEPES pH 7.5 and then crystallized by hanging drop vapor diffusion using 10 mM MES pH 6.0, 7.5 mM Sm(OAc)3, 4% dioxane, 10-20% PEG 8000 as the precipitating solution at 20°C. The structure is solved at a resolution of 33.0-1.9 A
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C65S
mutation targeting the Ref-1 redox functions. Mutant form is detected in cytoplasmic vesicles indicating altered turnover. The endonuclease domain of Ape1 is required for successful mitotic progression
D219A
replacement of Asp219 with alanine decreases both the DNA binding and the AP endonuclease activity of the enzyme compared to wild-type
D308A
replacement of Asp308 with alanine results in decrease in endonuclease activity, but the DNA binding activity is preserved compared to wild-type
D90A
replacement of Asp90 with alanine results in decrease in endonuclease activity, but the DNA binding activity is preserved compared to wild-type
E96A
replacement of Glu96 with alanine results in decrease in endonuclease activity, but the DNA binding activity is preserved compared to wild-type
E96Q
the mutant is expressed well in both TB and autoinducing media, the E96Q mutation prevents Mg2+ binding at this site
E96Q/D210N
mutation (APE1 ED or simply ED) is created by site-specific mutagenesis of the pETApe1 plasmid, mutant cannot bind Mg2+ in the active site
H309N
site-directed mutagenesis, the mutant still binds to chromatin and gets acetylated
K27Q
site-directed mutagenesis, chromatin-binding defective K27Q mutant, but the mutation of Lys27 in recombinant APE1 proteins does not affect acetylation by p300 at Lys6 in vitro
K6A/K7A
mutation targeting the gene regulation function. Mutant shows a diffuse nuclear staining, with a minimal localization in nucleoli. Mutant produces mitotic defects in Ape1-depleted cells, particularly promoting the formation of binucleated cells. Expression of the mutant protein increases the frequency of end-to-end fusions
N212A
N226A
increased cleavage rate at apurinic/apyrimidinic sites, ability to bind to damaged DNA decreases
N226A/N229A
ability of the mutant to bind damaged DNA is decreased, Vmax is almost identical to that of the wild-type enzyme
N229A
increased cleavage rate at apurinic/apyrimidinic sites, ability to bind to damaged DNA decreases
R177A
C118A
m6A demethylase activity similar to wild-type, about 25% decrease in apurinic/apyrimidinic lyase activity
C118A/C129A
about 50% decrease in m6A demethylase activity, about 20% decrease in apurinic/apyrimidinic lyase activity
C129A
about 90% decrease in m6A demethylase activity, about 30% decrease in apurinic/apyrimidinic lyase activity
C138A
-
stable Skov-3X cells with the NFB-Luc gene are cotransfected with plasmid pcDNA-mutant, mutant is redox active
C208A
-
stable Skov-3X cells with the NFB-Luc gene are cotransfected with plasmid pcDNA-mutant, mutant is redox active
C296A
-
stable Skov-3X cells with the NFB-Luc gene are cotransfected with plasmid pcDNA-mutant, mutant is redox active
C310A
-
stable Skov-3X cells with the NFB-Luc gene are cotransfected with plasmid pcDNA-mutant, mutant is redox active
C65A
C65A/C93A
-
mutant form of TAT-APE1 is generated by insertion of full-length of APE1 C65A/C93A into pTAT-2.1
C93A
-
stable Skov-3X cells with the NFB-Luc gene are cotransfected with plasmid pcDNA-mutant, mutant is redox active
C99A
-
stable Skov-3X cells with the NFB-Luc gene are cotransfected with plasmid pcDNA-mutant, mutant is redox active
C99S
-
the mutant loses affinity for DNA and its activity is inhibited by 10 mM Mg2+, involvement of Cys99 in APE1's substrate binding and catalysis provides an example of involvement of a residue far from the active site
D210N
D233A
no residual m6A demethylase activity, about 30% decrease in apurinic/apyrimidinic lyase activity
D283N
D308A
D70A
D70R
-
binding affinity nearly identical with wild-type enzyme, reduced specific endonuclease activity, at Mg2+ concentrations below 1 mM the activity of the mutant sharply decreases
DELTA1-29
-
mutant enzyme retains activity against abasic sites in single-stranded DNA
DELTA1-36
-
mutant enzyme retains activity against abasic sites in single-stranded DNA
E96A
E96Q
F266A
-
30fold reduction in abasic dsDNA incision, complete loss of endoribonuclease activity against c-myc CRD
F319A
DNA glycosylase activity is reduced 52.6fold, activity towards abasic sites is reduced 1.5fold
H113A/C118A/C129A/H134A
no residual m6A demethylase activity, about 55% decrease in apurinic/apyrimidinic lyase activity
H231A
no residual m6A demethylase activity, about 20% decrease in apurinic/apyrimidinic lyase activity
H270A
DNA glycosylase activity is reduced 50fold, activity towards abasic sites is reduced 2.3fold
H270L
DNA glycosylase activity is reduced 71.4fold, activity towards abasic sites is reduced 3.7fold
H270R
DNA glycosylase activity is reduced 3.9fold, activity towards abasic sites is nearly identical to wild-type activity
H287A
no residual m6A demethylase activity, about 25% decrease in apurinic/apyrimidinic lyase activity
H309N
InsG212
-
extended hairpin, diminished recognition and binding to 5-hydroxycytosine-containing DNA
K133A
about 50% decrease in m6A demethylase activity, about 45% decrease in apurinic/apyrimidinic lyase activity
K3l/R4L/K6L/K7L
-
as the wild-type enzyme the mutant enzyme is predominantly localitzed in the nucleus
K6R/K7R
-
no significant difference in nuclear localization between wild-type enzyme and mutant enzyme
N68A
P211R
-
kinetic parameters similar to wild-type enzyme, decreased specificity of binding
Q315A
DNA glycosylase activity is reduced 1.6fold, activity towards abasic sites is increased 1.18fold
Y128A
Y171A
-
enhancement by imidazole (in absence of tyrosine) is lower than that of wild-type enzyme. The ratio of turnover number to Km-value for DNA containing an abasic site is 50000fold lower than wild-type value at low salt concentration and 7500fold lower than wild-type value at high salt concentrations
Y171F
Y171F/P173L/N174K
-
mutation results in 20000fold decrease in the reaction rate and reduced binding affinity
Y171H
-
mutant enzyme is not enhanceed by imidazole (in absence of tyrosine). The ratio of turnover number to Km-value for DNA containing an abasic site is 50000fold lower than wild-type value at low salt concentration
Y269A
-
the ratio of turnover number to Km-value for DNA containing an abasic site is 12.5fold lower than wild-type value at low salt concentration and 21.4fold lower than wild-type value at high salt concentrations
additional information
N212A
mutation targeting the endonuclease function. Mutant shows mainly nuclear staining, with a focal accumulation in nucleoli. Expression of the mutant protein increases the frequency of end-to-end fusions
N212A
simulations with substitution of Asn212 by Ala show a Mg2+-ion coordination comparable to that of the wild-type
R177A
APE1's high affinity for DNA single-strand breaks requires Arg177, poly(ADP-ribose)polymerase 1, PARP1, activation is not suppressed by the mutant
R177A
he turnover number of the endonuclease reaction catalyzed by APE1 increases compared to wild-type when Arg177 is replaced by alanine
C65A
-
site-directed mutagenesis of a pET28A vector encoding human Ape1 (40-318) is performed, mutant is redox inactive
D210N
-
mutant enzyme is catalytically inactive against abasic sites in double-stranded DNA and single-stranded DNA
D210N
-
loss of abasic dsDNA incision, complete loss of endoribonuclease activity against c-myc CRD
D283N
-
loss of abasic dsDNA incision, no change in endoribonuclease activity against c-myc CRD
D283N
-
retaines endoribonuclease and abasic single-stranded RNA cleavage activities, with concurrent loss of apurinic/apyrimidinic site cleavage activities on double-stranded DNA and single-stranded DNA
D308A
-
1.4fold reduction in abasic dsDNA incision, complete loss of endoribonuclease activity against c-myc CRD
D70A
-
6.7fold reduction in abasic dsDNA incision, complete loss of endoribonuclease activity against c-myc CRD
E96A
-
APE-1 mutant displays a significantly reduced DNA-repair activity when compared with the wild-type protein
E96A
-
the mutant does not exhibit any nuclease activity against 88-nt RNA substrate
E96A
-
no reduction in abasic dsDNA incision, complete loss of endoribonuclease activity against c-myc CRD
E96Q
-
binding affinity nearly identical with wild-type enzyme, reduced specific endonuclease activity
H309N
-
the mutant does not exhibit any nuclease activity against 88-nt RNA substrate
N68A
-
binding affinity nearly identical with wild-type enzyme, reduced specific endonuclease activity, at Mg2+ concentrations below 1 mM the activity of the mutant sharply decreases
N68A
-
loss of abasic dsDNA incision, complete loss of endoribonuclease activity against c-myc CRD
Y128A
-
the ratio of turnover number to Km-value for DNA containing an abasic site is 33fold lower than wild-type value at low salt concentration and 7.5fold lower than wild-type value at high salt concentrations
Y171F
-
the ratio of turnover number to Km-value for DNA containing an abasic site is 25000fold lower than wild-type value at low salt concentration
Y171F
-
loss of abasic dsDNA incision, complete loss of endoribonuclease activity against c-myc CRD
additional information
APE1 lacking the first 34 amino acids at the Nterminus, unlike wild-type enzyme, is unable to form cross-links with BS-AP DNAs that testifies to the involvement of disordered N-terminal extension, which is enriched in lysine residues, in the interaction with AP sites.
additional information
-
APE1 lacking the first 34 amino acids at the Nterminus, unlike wild-type enzyme, is unable to form cross-links with BS-AP DNAs that testifies to the involvement of disordered N-terminal extension, which is enriched in lysine residues, in the interaction with AP sites.
additional information
apurinic/apyrimidinic endonuclease 1-siRNA-mediated downregulation in osteosarcoma cells inhibits expression of TGFbeta1. Apurinic/apyrimidinic endonuclease 1-siRNA inhibits the capability to enhance HUVEC migration and tube formation of tumor cells through the TGFbeta/Smad3 signaling pathway. Tumor angiogenesis and growth in xenografts are suppressed by APE1-siRNA
additional information
-
apurinic/apyrimidinic endonuclease 1-siRNA-mediated downregulation in osteosarcoma cells inhibits expression of TGFbeta1. Apurinic/apyrimidinic endonuclease 1-siRNA inhibits the capability to enhance HUVEC migration and tube formation of tumor cells through the TGFbeta/Smad3 signaling pathway. Tumor angiogenesis and growth in xenografts are suppressed by APE1-siRNA
additional information
construction of a redox-deficient truncated APE1 protein lacking the first N-terminal 61 amino acid residues (APE1-NDELTA61) the mutant cannot stimulate DNA glycosylase activities of OGG1, MBD4, and ANPG on duplex DNA substrates in contrast to the wild-type enzyme
additional information
-
construction of a redox-deficient truncated APE1 protein lacking the first N-terminal 61 amino acid residues (APE1-NDELTA61) the mutant cannot stimulate DNA glycosylase activities of OGG1, MBD4, and ANPG on duplex DNA substrates in contrast to the wild-type enzyme
additional information
downregulation of endogenous APE1 levels in HEK293T cells using small interfering RNA (siRNA). Mutant phenotypes, overview
additional information
-
downregulation of endogenous APE1 levels in HEK293T cells using small interfering RNA (siRNA). Mutant phenotypes, overview
additional information
protein with two additional amino acid residues and a truncated protein with deletion of 22 residues at the amino-terminus are equally active
additional information
-
protein with two additional amino acid residues and a truncated protein with deletion of 22 residues at the amino-terminus are equally active
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
lowering the pH to 4.5 simply protonated H309 and makes it unsuitable for metal binding
692773
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Mg2+ ions stabilize the protein structure and the enzyme-substrate complex
under base excision repair conditions, the REF1 domain of APE1 influences the stability of both the enzyme-substrate and enzyme-product complexes, as well as the isomerization rate, but does not affect the rates of initial complex formation or catalysis
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Clear supernatant from cell extract is applied to two columns in series: a strong anion exchange column (Q-Sepharose) followed by a strong cation exchange (HS50). After sample loading, both columns are washed with buffer and then the Q-Sepharose column is disconnected. APE1 bound in the HS50 column is eluted with a 50-700 mM KCl gradient. Clean APE1 fractions are pooled and then dialyzed extensively in buffer to remove glycerol, elution salts, and metal ions, followed by two runs of dialysis with EDTA-free buffer. Average yield of APE1 is 200 mg out of 15 g of cells
His-tagged APE1 is purified from Escherichia coli M15 cells by using Ni-affinity chromatography with Swell-gel Nickel-chelated discs
recombinant enzyme from Escherichia coli strain Rosetta II(DE3)
recombinant enzyme from Escherichia coli strain Rosetta II(DE3) by anion exchange chromatography, dialysis, cation exchange chromatography, dialysis, and hydrophobic interaction chromatography
after affinity purification and cleavage of the His-tag, the untagged proteins to near homogeneity are purified by fast protein liquid chromatography using heparin-sepharose
-
APE-1 proteins partially purified purified are visualized by Western blot using anti-human APE-1 antibody
-
Bacteria are lyzed in a denaturing buffer (50 mmol NaCl and phosphate pH 7.5, 4 mol urea), the His-hNTH1 protein is purified by chromatography on a nickel column followed by gel filtration on a Superdex-200 column. The TAP-hNTH1 protein is purified from a stable MCF-7 clone expressing this protein construct with a TAP purification kit.
-
by ammonium sulfate precipitation and affinity chromatography, using a HiTrap chelating column, charged with Ni2+, and a HiTrap heparin column
-
full-length recombinant CSB and APE1 proteins are expressed and purified, used in direct and indirect ELISAs
-
histidine-tagged AP endonucleases are purified on Ni2+-charged HiTrap Chelating HP columns
-
Purification is done using the standard glutathione affinity purification protocol. The C65A mutant is purified as follows: cell suspension is centrifuged, supernatant is loaded on a Ni-NTA column and the protein is eluted with a linear imidazole gradient. Fractions containing C65A hApe1 are further purified on an S-Sepharose column with a linear NaCl gradient.
-
recombinant human full-length and Ndelta33 APE1 is purified using a Ni-NTA Superflow and a SP-Sepharose column
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
ectopical expression of FLAG-tagged wild-type APE1 and mutants K27Q or H309N in HEK-293T cell with downregulated endogenous APE1
gene APE1, recombinant expression of enzyme in Escherichia coli strain Rosetta II(DE3)
gene APE1, recombinant expression of the enzyme in Escherichia coli strain Rosetta II(DE3)
recombinant enzyme expression in Escherichia coli strain Rosetta II(DE3)
Recombinant human APE1 protein is overexpressed from clone pETApe1 in Escherichia coli BL21(DE3)
adenoviruses full-length APE1/Ref-1 (AdAPE1/Ref-1) is generated by homologous recombination in human embryonic kidney 293 cells. Human umbilical vein endothelial cells are infected with 200 multiplicity of infection
-
fusion protein with glutathione S-transferase
Generation of random mutations in the ape1 gene and selection of variants that confer protection against H2O2. Random library of ape1 mutants is generated by transforming the mutator strain XL1-Red with the prokaryotic ape1 plasmid pKK-ape1. The H2O2-resistant phenotype (mutant D70A) is expressed in Escherichia coli strain BW528 (xth nfo), which is deficient in the major AP endonucleases, exonuclease III and endonuclease IV
-
Human Ape1/Ref-1 cDNA is amplified by RT-PCR using Ape1/Ref-1-specific primers and from human GM00637 fibroblasts. AP endonuclease domain deletion mutant deltaAPD is amplified by RT-PCR using specific primers from full length human Ape1/Ref-1 cDNA. Redox domain deletion mutant deltaRD is amplified by RT-PCR using specific primers from full length human Ape1/Ref-1 cDNA.
-
into various expression plasmids for GFP, GST or His-tag, for expression in Escherichia coli cells
-
RKO cell lines are established, that can be induced by doxycycline to overexpress APE-1 wild-type, mutant C65A, mutant E96A or mutant E96Q
-
The human NTH1 cDNA is cloned into the PCRII plasmid and it is cloned into the EcoRI site of the pGEX-2TK vector. The hNTH1 cDNA is cut (amino acids 1-94) and cloned into the modified restriction sites in the pGEX-2TK vector. The remaining fragment (amino acids 95-312) is cloned into the pGEX-3X vector. The hNTH1 cDNA is cloned into the pET24d vector in-frame with the His-tag and into the pNTAP-B vector in-frame with the TAP-epitope. To knock down the expression of Y-box-binding protein-1, a hairpin sequence specific to Y-box-binding protein-1 is cloned into the pSuper vector. His-hNTH1 protein is produced in the BL21 bacterial strain. MCF-7 cells are transfected with a siRNA specific to hNTH1.
-
The wild-type and mutant hApe1 proteins are expressed as GST-fusions in Escherichia coli
-
wild-type APE1 and its Cys mutants are expressed as His-tag fusion polypeptides in Escherichia coli
-
wild-type APE1 encoding full-length of APE1 and APE1 C65A/C93A encoding mutant form of APE1 in pCMVTag2B mammalian expression vector are generated by standard cloning method. TAT-APE1 is generated by insertion of full-length of APE1 into pTAT-2.1
-
recombinant enzyme expression in Escherichia coli strain Rosetta II(DE3)
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
level of expression of the gene encoding APE1 increases under oxidative stress
Helicobacter pylori infection induces apoptosis and increases APE-1 expression in human gastric epithelial cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
APE1/Ref-1 expression levels together with subcellular dysregulation may be predictive markers to indicate the tumor sensitivity toward radiotherapy or chemotherapy
drug development
medicine
comparison of mouse and human enzyme. Overall results suggest that human and mouse APE1s have mostly similar biochemical and biophysical properties. The conclusions of mouse studies to elucidate APE1 biology and its role in carcinogenesis may be extrapolated to apply to human biology
analysis
drug development
medicine
additional information
drug development
APE1 is an attractive therapeutic target in anticancer drug development, there is a link of APE1 overexpression in many cancers to resistance of tumor cells to radio- and chemotherapy. APE1 shows a protective effect in several cancer cell models to a variety of DNA damaging agents.
drug development
strategies to modulate the proteolytic removal of the APE1 n-terminus will constitute a possible good candidate target for future drug development
analysis
-
chemical footprinting-mass spectrometric assay using N-ethylmaleimide, an irreversible Cys modifier, to characterize the interaction of the redox inhibitor, E3330, with APE1. When APE1 is incubated with E3330, two N-ethylmaleimide-modified products are observed, one with two and a second with seven added N-ethylmaleimide molecules
analysis
-
development an effective in vitro system for monitoring G quadruplex structure formation in damage-containing DNA, a tool to investigate the mechanistic details of repair occurring at this noncanonical DNA structure
analysis
development of assay method using a methylation-sensitive restriction endonuclease
drug development
-
cancer therapy, human endonuclease III enzyme is a relevant target to potentiate cisplatin cytotoxicity in Y-box binding protein-1 overexpressing tumor cells
drug development
-
inhibition of AP endonuclease may be effective in decreasing the dose requirements of chemotherapeutics used in the treatment of cancer as well as other diseases.
medicine
-
a decrease in APE1 levels in silencing RNA-treated osteogenic sarcoma cells leads to enhanced cell sensitization to the DNA damaging agents: methyl methanesulfonate, H2O2, ionizing radiation and chemotherapeutic agents
medicine
-
the APE-mediated decrease in expression of MSH6 protein results in a reduced cellular mismatch repair capacity as well as the increased generation of microsatellite instability. The potential role of APE to generate microsatellite instability may have clinically important implications for cancer susceptibility and carcinogenesis
medicine
-
after catalytically enzymatic activity or expression of APE is decreased, antiviral activity of APOBEC3G is partially inhibited in virus-producing cells
medicine
-
APE-1 exonuclease activity plays an important role in the removal of L-configuration nucleoside analogs from DNA inside the cell and can be a determining factor in the drug resistance of the analogs
medicine
-
APE-1/Ref-1 is an important regulator of gastric epithelial responses to Helicobacter pylori infections
medicine
-
downregulation of APE1 is found to sensitize tumor cells to chemotherapy with induction of apoptosis
medicine
-
selective targeting of APE1/Ref-1 could enhance conventional cancer treatment such as radiotherapy
medicine
-
leading therapeutic target molecule for the oxidative stress condition or pathologic conditions such as cancer. Increased levels of APE1/Ref-1 in tumors have been associated greater resistance to chemotherapy and carry a poorer prognosis
medicine
-
levels of APE-1 expression in gastric and other cancer tissues may be used to determine chemosensitivity
medicine
-
strong candidate as a potential drug-treatable target for the prevention and treatment of human melanoma
medicine
-
APE1 is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers
medicine
-
patients with tumors containing elevated cytoplasmic Ape1 have a poor prognosis and a 3.722fold risk of tumor recurrence and/or metastasis
additional information
enzyme APE1 is a promising target for the development of small-molecule inhibitors to be used in combination with anticancer agents
additional information
-
enzyme APE1 is a promising target for the development of small-molecule inhibitors to be used in combination with anticancer agents
REF.
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TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Shaper, N.L.; Grafstrom, R.H.; Grossman, L.
Human placental apurinic/apyrimidinic endonuclease. Its isolation and characterization
J. Biol. Chem.
257
13455-13458
1982
Homo sapiens
Brent, T.P.
Properties of a human lymphoblast AP-endonuclease asociated with activity for DAN damaged by ultraviolet light, gamma-rays, or osmium tetroxide
Biochemistry
22
4507-4512
1983
Homo sapiens
Robson, C.N.; Hickson, I.D.
Isolation of cDNA clones encoding a human apurinic/apyrimidinic endonuclease that corrects DNA repair and mutagenesis defects in E. coli xth (exonuclease III) mutants
Nucleic Acids Res.
19
5519-5523
1991
Homo sapiens (P27695), Homo sapiens
Demple, B.; Herman, T.; Chen, D.S.
Cloning and expression of APE, the cDNA encoding the major human apurinic exonuclease: definition of a family of DNA repair enzymes
Proc. Natl. Acad. Sci. USA
88
11450-11454
1991
Homo sapiens (P27695), Homo sapiens
Cheng, X.; Bunville, J.; Patterson, T.A.
Nucleotide sequence of cDNA for a apurinic/apyrimidinic endonuclease from HeLa cells
Nucleic Acids Res.
20
370
1992
Homo sapiens (P27695)
Warner, H.R.; Persson, M.L.; Bensen, R.J.; Mosbaugh, D.W.; Linn, S.
Selective inhibition by harmane of apurinic/apyrimidinic endonuclease activity of phage T4-induced UV endonuclease
Nucleic Acids Res.
9
6083-6092
1981
Tequatrovirus T4, Escherichia coli, Homo sapiens
Grafstrom, R.H.; Shaper, N.L.; Grossman, L.
Human placental apurinic/apyrimidinic endonuclease. Mechanism of action
J. Biol. Chem.
257
13459-13464
1982
Homo sapiens
Aburatani, H.; Hippo, Y.; Ishida, T.; Takashima, R.; Matsuba, C.; Kodama, T.; Takao, M.; Yasui, A.; Yamamoto, K.; Asano, M.
Cloning and characterization of mammalian 8-hydroxyguanine-specific DNA glycosylase/apurinic, apyrimidinic lyase, a functional mutM homologue
Cancer Res.
57
2151-2156
1997
Homo sapiens (O15527)
Beloglazova, N.G.; Petruseva, I.O.; Bulychev, N.V.; Maksakova, G.A.; Johnson, F.; Nevinskii, G.A.
Isolation and substrate specificity of apurinic/apyrimidinic endonuclease from human placenta
Mol. Biol.
31
946-951
1997
Homo sapiens
Chaudhry, M.A.; Weinfeld, M.
Reactivity of human apurinic/apyrimidinic endonuclease and Escherichia coli exonuclease III with bistranded abasic sites in DNA
J. Biol. Chem.
272
15650-15655
1997
Escherichia coli, Homo sapiens
Eide, L.; Luna, L.; Gustad, E.C.; Henderson, P.T.; Essigmann, J.M.; Demple, B.; Seeberg, E.
Human endonuclease III acts preferentially on DNA damage opposite guanine residues in DNA
Biochemistry
40
6653-6659
2001
Homo sapiens
Grosch, S.; Kaina, B.
Transcriptional activation of apurinic/apyrimidinic endonuclease (Ape, Ref-1) by oxidative stress requires CREB
Biochem. Biophys. Res. Commun.
261
859-863
1999
Homo sapiens
Hilbert, T.P.; Chaung, W.; Boorstein, R.J.; Cunningham, R.P.; Teebor, G.W.
Cloning and expression of the cDNA encoding the human homolog of the DNA repair enzyme, Escherichia coli endonuclease III
J. Biol. Chem.
272
6733-6740
1997
Homo sapiens (P78549), Homo sapiens
Ikeda, S.; Biswas, T.; Roy, R.; Izumi, T.; Boldogh, I.; Kurosky, A.; Sarker, A.H.; Seki, S.; Mitra, S.
Purification and characterization of human NTH1, a homolog of Escherichia coli endonuclease III. Direct identification of Lys-212 as the active nucleophilic residue
J. Biol. Chem.
273
21585-21593
1998
Homo sapiens (P78549), Homo sapiens
Lebedeva, N.A.; Khodyreva, S.N.; Favre, A.; Lavrik, O.I.
AP endonuclease 1 has no biologically significant 3'->5'-exonuclease activity
Biochem. Biophys. Res. Commun.
300
182-187
2002
Homo sapiens
Lucas, J.A.; Masuda, Y.; Bennett, R.A.O.; Strauss, N.S.; Strauss, P.R.
Single-turnover analysis of mutant human apurinic/apyrimidinic endonuclease
Biochemistry
38
4958-4964
1999
Homo sapiens
Marenstein, D.R.; Chan, M.K.; Altamirano, A.; Basu, A.K.; Boorstein, R.J.; Cunningham, R.P.; Teebor, G.W.
Substrate specificity of human endonuclease III (hNTH1). Effect of human APE1 on hNTH1 activity
J. Biol. Chem.
278
9005-9012
2003
Homo sapiens
Mguyen, L.H.; Barsky, D.; Erzberger, J.P.; Wilson, D.M., 3rd
Mapping the protein-DNA interface and the metal-binding site of the major human apurinic/apyrimidinic endonuclease
J. Mol. Biol.
298
447-459
2000
Homo sapiens
Micolas, E.; Beggs, J.M.; Haltiwanger, B.M.; Taraschi, T.F.
A new class of DNA glycosylase/apurinic/apyrimidinic lyases that act on specific adenines in single-stranded DNA
J. Biol. Chem.
273
17216-17220
1998
Homo sapiens
Pope, M.A.; Porello, S.L.; David, S.S.
Escherichia coli apurinic-apyrimidinic endonucleases enhance the turnover of the adenine glycosylase MutY with G:A substrates
J. Biol. Chem.
277
22605-22615
2002
Escherichia coli, Homo sapiens
Tom, S.; Ranalli, T.A.; Podust, V.N.; Bambara, R.A.
Regulatory roles of p21 and apurinic/apyrimidinic endonuclease 1 in base excision repair
J. Biol. Chem.
276
48781-48789
2001
Homo sapiens
Xu, Y.j.; DeMott, M.S.; Hwang, J.T.; Greenberg, M.M.; Demple, B.
Action of human apurinic endonuclease (Ape1) on C1'-oxidized deoxyribose damage in DNA
DNA Repair
2
175-185
2003
Homo sapiens
Xu, Y.j.; Kim, E.Y.; Demple, B.
Excision of C-4'-oxidized deoxyribose lesions from double-stranded DNA by human apurinic/apyrimidinic endonuclease (Ape1 protein) and DNA polymerase b
J. Biol. Chem.
273
28837-28844
1998
Homo sapiens
Yoshida, A.; Ueda, T.
Human AP endonuclease possesses a significant activity as major 3'-5' exonuclease in human leukemia cells
Biochem. Biophys. Res. Commun.
310
522-528
2003
Homo sapiens
Luo, M.; Kelley, M.R.
Inhibition of the human apurinic/apyrimidinic endonuclease (APE1) repair activity and sensitization of breast cancer cells to DNA alkylating agents with lucanthone
Anticancer Res.
24
2127-2134
2004
Homo sapiens
Izumi, T.; Schein, C.H.; Oezguen, N.; Feng, Y.; Braun, W.
Effects of backbone contacts 3' to the abasic site on the cleavage and the product binding by human apurinic/apyrimidinic endonuclease (APE1)
Biochemistry
43
684-689
2004
Homo sapiens (P27695), Homo sapiens
Mundle, S.T.; Fattal, M.H.; Melo, L.F.; Coriolan, J.D.; O'Regan, N.E.; Strauss, P.R.
Novel role of tyrosine in catalysis by human AP endonuclease 1
DNA Repair
3
1447-1455
2004
Homo sapiens
Marenstein, D.R.; Wilson, D.M., 3rd; Teebor, G.W.
Human AP endonuclease (APE1) demonstrates endonucleolytic activity against AP sites in single-stranded DNA
DNA Repair
3
527-533
2004
Homo sapiens
Ali, M.M.; Hazra, T.K.; Hong, D.; Kow, Y.W.
Action of human endonucleases III and VIII upon DNA-containing tandem dihydrouracil
DNA Repair
4
679-686
2005
Homo sapiens
Xia, L.; Zheng, L.; Lee, H.W.; Bates, S.E.; Federico, L.; Shen, B.; O'Connor, T.R.
Human 3-methyladenine-DNA glycosylase: effect of sequence context on excision, association with PCNA, and stimulation by AP endonuclease
J. Mol. Biol.
346
1259-1274
2005
Homo sapiens
Wang, D.; Luo, M.; Kelley, M.R.
Human apurinic endonuclease 1 (APE1) expression and prognostic significance in osteosarcoma: enhanced sensitivity of osteosarcoma to DNA damaging agents using silencing RNA APE1 expression inhibition
Mol. Cancer Ther.
3
679-686
2004
Homo sapiens
Beloglazova, N.G.; Kirpota, O.O.; Starostin, K.V.; Ishchenko, A.A.; Yamkovoy, V.I.; Zharkov, D.O.; Douglas, K.T.; Nevinsky, G.A.
Thermodynamic, kinetic and structural basis for recognition and repair of abasic sites in DNA by apurinic/apyrimidinic endonuclease from human placenta
Nucleic Acids Res.
32
5134-5146
2004
Homo sapiens
van der Kemp, P.A.; Charbonnier, J.B.; Audebert, M.; Boiteux, S.
Catalytic and DNA-binding properties of the human Ogg1 DNA N-glycosylase/AP lyase: biochemical exploration of H270, Q315 and F319, three amino acids of the 8-oxoguanine-binding pocket
Nucleic Acids Res.
32
570-578
2004
Homo sapiens (O15527), Homo sapiens
Gros, L.; Ishchenko, A.A.; Ide, H.; Elder, R.H.; Saparbaev, M.K.
The major human AP endonuclease (Ape1) is involved in the nucleotide incision repair pathway
Nucleic Acids Res.
32
73-81
2004
Homo sapiens
Sukhanova, M.V.; Khodyreva, S.N.; Lebedeva, N.A.; Prasad, R.; Wilson, S.H.; Lavrik, O.I.
Human base excision repair enzymes apurinic/apyrimidinic endonuclease 1 (APE1), DNA polymerase b and poly(ADP-ribose) polymerase 1: interplay between strand-displacement DNA synthesis and proofreading exonuclease activity
Nucleic Acids Res.
33
1222-1229
2005
Homo sapiens
Jackson, E.B.; Theriot, C.A.; Chattopadhyay, R.; Mitra, S.; Izumi, T.
Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1)
Nucleic Acids Res.
33
3303-3312
2005
Homo sapiens
Chang, I.Y.; Kim, S.H.; Cho, H.J.; Lee do, Y.; Kim, M.H.; Chung, M.H.; You, H.J.
Human AP endonuclease suppresses DNA mismatch repair activity leading to microsatellite instability
Nucleic Acids Res.
33
5073-5081
2005
Homo sapiens
Dyrkheeva, N.S.; Lomzov, A.A.; Pyshnyi, D.V.; Khodyreva, S.N.; Lavrik, O.I.
Efficiency of exonucleolytic action of apurinic/apyrimidinic endonuclease 1 towards matched and mismatched dNMP at the 3 terminus of different oligomeric DNA structures correlates with thermal stability of DNA duplexes
Biochim. Biophys. Acta
1764
699-706
2006
Homo sapiens
Raffoul, J.J.; Banerjee, S.; Singh-Gupta, V.; Knoll, Z.E.; Fite, A.; Zhang, H.; Abrams, J.; Sarkar, F.H.; Hillman, G.G.
Down-regulation of apurinic/apyrimidinic endonuclease 1/redox factor-1 expression by soy isoflavones enhances prostate cancer radiotherapy in vitro and in vivo
Cancer Res.
67
2141-2149
2007
Homo sapiens, Mus musculus
Sidorenko, V.S.; Nevinsky, G.A.; Zharkov, D.O.
Mechanism of interaction between human 8-oxoguanine-DNA glycosylase and AP endonuclease
DNA Repair
6
317-328
2007
Homo sapiens
Kanno, S.; Kuzuoka, H.; Sasao, S.; Hong, Z.; Lan, L.; Nakajima, S.; Yasui, A.
A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses
EMBO J.
26
2094-2103
2007
Homo sapiens
Yang, B.; Chen, K.; Zhang, C.; Huang, S.; Zhang, H.
Virion-associated uracil DNA glycosylase-2 and apurinic/apyrimidinic endonuclease are involved in the degradation of APOBEC3G-edited nascent HIV-1 DNA
J. Biol. Chem.
282
11667-11675
2007
Homo sapiens
Liu, Y.; Prasad, R.; Beard, W.A.; Kedar, P.S.; Hou, E.W.; Shock, D.D.; Wilson, S.H.
Coordination of steps in single-nucleotide base excision repair mediated by apurinic/apyrimidinic endonuclease 1 and DNA polymerase beta
J. Biol. Chem.
282
13532-13541
2007
Homo sapiens
Maher, R.L.; Bloom, L.B.
Pre-steady-state kinetic characterization of the AP endonuclease activity of human AP endonuclease 1
J. Biol. Chem.
282
30577-30585
2007
Homo sapiens
Adhikari, S.; Uren, A.; Roy, R.
Dipole-dipole interaction stabilizes the transition state of apurinic/apyrimidinic endonuclease-abasic site interaction
J. Biol. Chem.
283
1334-1339
2008
Homo sapiens
OHara, A.M.; Bhattacharyya, A.; Mifflin, R.C.; Smith, M.F.; Ryan, K.A.; Scott, K.G.; Naganuma, M.; Casola, A.; Izumi, T.; Mitra, S.; Ernst, P.B.; Crowe, S.E.
Interleukin-8 induction by Helicobacter pylori in gastric epithelial cells is dependent on apurinic/apyrimidinic endonuclease-1/redox factor-1
J. Immunol.
177
7990-7999
2006
Homo sapiens
Lam, W.; Park, S.Y.; Leung, C.H.; Cheng, Y.C.
Apurinic/apyrimidinic endonuclease-1 protein level is associated with the cytotoxicity of L-configuration deoxycytidine analogs (troxacitabine and beta-L-2,3-dideoxy-2,3-didehydro-5-fluorocytidine) but not D-configuration deoxycytidine analogs
Mol. Pharmacol.
69
1607-1614
2006
Homo sapiens
Chattopadhyay, R.; Wiederhold, L.; Szczesny, B.; Boldogh, I.; Hazra, T.K.; Izumi, T.; Mitra, S.
Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells
Nucleic Acids Res.
34
2067-2076
2006
Homo sapiens, Bos taurus (P23196), Bos taurus
Wong, H.K.; Muftuoglu, M.; Beck, G.; Imam, S.Z.; Bohr, V.A.; Wilson, D.M.
Cockayne syndrome B protein stimulates apurinic endonuclease 1 activity and protects against agents that introduce base excision repair intermediates
Nucleic Acids Res.
35
4103-4113
2007
Homo sapiens
Zaky, A.; Busso, C.; Izumi, T.; Chattopadhyay, R.; Bassiouny, A.; Mitra, S.; Bhakat, K.K.
Regulation of the human AP-endonuclease (APE1/Ref-1) expression by the tumor suppressor p53 in response to DNA damage
Nucleic Acids Res.
36
1555-1566
2008
Homo sapiens
Peddi, S.R.; Chattopadhyay, R.; Naidu, C.V.; Izumi, T.
The human apurinic/apyrimidinic endonuclease-1 suppresses activation of poly(adp-ribose) polymerase-1 induced by DNA single strand breaks
Toxicology
224
44-55
2006
Homo sapiens (P27695), Homo sapiens
Jeon, B.H.; Irani, K.
APE1/Ref-1: Versatility in Progress
Antioxid. Redox Signal.
11
571-573
2008
Homo sapiens
Yuk, J.M.; Yang, C.S.; Shin, D.M.; Kim, K.K.; Lee, S.K.; Song, Y.J.; Lee, H.M.; Cho, C.H.; Jeon, B.H.; Jo, E.K.
A Dual Regulatory Role of Apurinic/apyrimidinic Endonuclease 1/Redox Factor-1 in HMGB1-induced Inflammatory Responses
Antioxid. Redox Signal.
11
575-587
2008
Homo sapiens
Tell, G.; Quadrifoglio, F.; Tiribelli, C.; Kelley, M.R.
The Many Functions of APE1/Ref-1: Not Only a DNA Repair Enzyme
Antioxid. Redox Signal.
11
601-619
2008
Homo sapiens (P27695)
Yang, S.; Meyskens, F.L.
Apurinic/apyrimidinic endonuclease /redox effector factor-1 (APE/Ref-1) a unique target for the prevention and treatment of human melanoma
Antioxid. Redox Signal.
11
639-650
2008
Homo sapiens
Park, W.S.; Ko, E.A.; Jung, I.D.; Son, Y.K.; Kim, H.K.; Kim, N.; Park, S.Y.; Hong, K.W.; Park, Y.M.; Choi, T.H.; Han, J.
APE1/Ref-1 promotes the effect of angiotensin II on Ca2+-activated K+ channel in human endothelial cells via suppression of NADPH oxidase
Arch. Pharm. Res.
31
1291-1301
2008
Homo sapiens
Mundle, S.T.; Delaney, J.C.; Essigmann, J.M.; Strauss, P.R.
Enzymatic mechanism of human apurinic/apyrimidinic endonuclease against a THF AP site model substrate
Biochemistry
48
19-26
2009
Homo sapiens
Guay, D.; Garand, C.; Reddy, S.; Schmutte, C.; Lebel, M.
The human endonuclease III enzyme is a relevant target to potentiate cisplatin cytotoxicity in Y-box-binding protein-1 overexpressing tumor cells
Cancer Sci.
99
762-769
2008
Homo sapiens
Futagami, S.; Hiratsuka, T.; Shindo, T.; Horie, A.; Hamamoto, T.; Suzuki, K.; Kusunoki, M.; Miyake, K.; Gudis, K.; Crowe, S.E.; Tsukui, T.; Sakamoto, C.
Expression of apurinic/apyrimidinic endonuclease-1 (APE-1) in H. pylori-associated gastritis, gastric adenoma, and gastric cancer
Helicobacter
13
209-218
2008
Homo sapiens
Lipton, A.S.; Heck, R.W.; Primak, S.; McNeill, D.R.; Wilson, D.M.; Ellis, P.D.
Characterization of Mg2+ binding to the DNA repair protein apurinic/apyrimidic endonuclease 1 via solid-state 25Mg NMR spectroscopy
J. Am. Chem. Soc.
130
9332-9341
2008
Homo sapiens (P27695)
Zhao, J.; Gao, F.; Zhang, Y.; Wei, K.; Liu, Y.; Deng, X.
Bcl2 inhibits abasic site repair by down-regulating APE1 endonuclease activity
J. Biol. Chem.
283
9925-9932
2008
Homo sapiens
Zawahir, Z.; Dayam, R.; Deng, J.; Pereira, C.; Neamati, N.
Pharmacophore guided discovery of small-molecule human apurinic/apyrimidinic endonuclease 1 inhibitors
J. Med. Chem.
52
20-32
2009
Homo sapiens (P27695), Homo sapiens
Berquist, B.R.; McNeill, D.R.; Wilson, D.M.
Characterization of abasic endonuclease activity of human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision
J. Mol. Biol.
379
17-27
2008
Homo sapiens
Mantha, A.K.; Oezguen, N.; Bhakat, K.K.; Izumi, T.; Braun, W.; Mitra, S.
Unusual role of a cysteine residue in substrate binding and activity of human AP-endonuclease 1
J. Mol. Biol.
379
28-37
2008
Homo sapiens
Kim, M.H.; Kim, H.B.; Acharya, S.; Sohn, H.M.; Jun, J.Y.; Chang, I.Y.; You, H.J.
Ape1/Ref-1 induces GDNF responsiveness by upregulating GFRalpha1 expression
Mol. Cell. Biol.
29
2264-2277
2009
Homo sapiens
Georgiadis, M.M.; Luo, M.; Gaur, R.K.; Delaplane, S.; Li, X.; Kelley, M.R.
Evolution of the redox function in mammalian apurinic/apyrimidinic endonuclease
Mutat. Res.
643
54-63
2008
Danio rerio, Homo sapiens
Castillo-Acosta, V.M.; Ruiz-Perez, L.M.; Yang, W.; Gonzalez-Pacanowska, D.; Vidal, A.E.
Identification of a residue critical for the excision of 3-blocking ends in apurinic/apyrimidinic endonucleases of the Xth family
Nucleic Acids Res.
37
1829-1842
2009
Homo sapiens, Leishmania major
Kim, S.E.; Gorrell, A.; Rader, S.D.; Lee, C.H.
Endoribonuclease activity of human apurinic/apyrimidinic endonuclease 1 revealed by a real-time fluorometric assay
Anal. Biochem.
398
69-75
2010
Homo sapiens, Rattus norvegicus
Bhakat, K.; Mantha, A.; Mitra, S.
Transcriptional regulatory functions of mammalian AP-endonuclease (APE1/Ref-1), an essential multifunctional protein
Antioxid. Redox Signal.
11
621-637
2009
Homo sapiens
Baldwin, M.R.; OBrien, P.J.
Human AP endonuclease 1 stimulates multiple-turnover base excision by alkyladenine DNA glycosylase
Biochemistry
48
6022-6033
2009
Homo sapiens
Al-Attar, A.; Gossage, L.; Fareed, K.R.; Shehata, M.; Mohammed, M.; Zaitoun, A.M.; Soomro, I.; Lobo, D.N.; Abbotts, R.; Chan, S.; Madhusudan, S.
Human apurinic/apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers
Br. J. Cancer
102
704-709
2010
Homo sapiens
Chattopadhyay, R.; Bhattacharyya, A.; Crowe, S.E.
Dual regulation by apurinic/apyrimidinic endonuclease-1 inhibits gastric epithelial cell apoptosis during Helicobacter pylori infection
Cancer Res.
70
2799-2808
2010
Homo sapiens
Harris, J.L.; Jakob, B.; Taucher-Scholz, G.; Dianov, G.L.; Becherel, O.J.; Lavin, M.F.
Aprataxin, poly-ADP ribose polymerase 1 (PARP-1) and apurinic endonuclease 1 (APE1) function together to protect the genome against oxidative damage
Hum. Mol. Genet.
18
4102-4117
2009
Homo sapiens
Li, M.; Zhong, Z.; Zhu, J.; Xiang, D.; Dai, N.; Cao, X.; Qing, Y.; Yang, Z.; Xie, J.; Li, Z.; Baugh, L.; Wang, G.; Wang, D.
Identification and characterization of mitochondrial targeting sequence of human apurinic/apyrimidinic endonuclease 1
J. Biol. Chem.
285
14871-14881
2010
Homo sapiens
Timofeyeva, N.A.; Koval, V.V.; Knorre, D.G.; Zharkov, D.O.; Saparbaev, M.K.; Ishchenko, A.A.; Fedorova, O.S.
Conformational dynamics of human AP endonuclease in base excision and nucleotide incision repair pathways
J. Biomol. Struct. Dyn.
26
637-652
2009
Homo sapiens
Lee, H.M.; Yuk, J.M.; Shin, D.M.; Yang, C.S.; Kim, K.K.; Choi, D.K.; Liang, Z.L.; Kim, J.M.; Jeon, B.H.; Kim, C.D.; Lee, J.H.; Jo, E.K.
Apurinic/apyrimidinic endonuclease 1 is a key modulator of keratinocyte inflammatory responses
J. Immunol.
183
6839-6848
2009
Homo sapiens
Bapat, A.; Glass, L.S.; Luo, M.; Fishel, M.L.; Long, E.C.; Georgiadis, M.M.; Kelley, M.R.
Novel small molecule inhibitor of Ape1 endonuclease blocks proliferation and reduces viability of glioblastoma cells
J. Pharmacol. Exp. Ther.
334
988-998
2010
Homo sapiens
Curtis, C.D.; Thorngren, D.L.; Ziegler, Y.S.; Sarkeshik, A.; Yates, J.R.; Nardulli, A.M.
Apurinic/apyrimidinic endonuclease 1 alters estrogen receptor activity and estrogen-responsive gene expression
Mol. Endocrinol.
23
1346-1359
2009
Homo sapiens
Roberts, S.A.; Strande, N.; Burkhalter, M.D.; Strom, C.; Havener, J.M.; Hasty, P.; Ramsden, D.A.
Ku is a 5-dRP/AP lyase that excises nucleotide damage near broken ends
Nature
464
1214-1217
2010
Homo sapiens
Barnes, T.; Kim, W.C.; Mantha, A.K.; Kim, S.E.; Izumi, T.; Mitra, S.; Lee, C.H.
Identification of apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA
Nucleic Acids Res.
37
3946-3958
2009
Homo sapiens, Rattus norvegicus
Wu, H.H.; Cheng, Y.W.; Chang, J.T.; Wu, T.C.; Liu, W.S.; Chen, C.Y.; Lee, H.
Subcellular localization of apurinic endonuclease 1 promotes lung tumor aggressiveness via NF-kappaB activation
Oncogene
29
4330-4340
2010
Homo sapiens
Simeonov, A.; Kulkarni, A.; Dorjsuren, D.; Jadhav, A.; Shen, M.; McNeill, D.R.; Austin, C.P.; Wilson, D.M.
Identification and characterization of inhibitors of human apurinic/apyrimidinic endonuclease APE1
PLoS ONE
4
e5740
2009
Homo sapiens
Yu, E.; Gaucher, S.P.; Hadi, M.Z.
Probing conformational changes in Ape1 during the progression of base excision repair
Biochemistry
49
3786-3796
2010
Homo sapiens
Kanazhevskaya, L.Y.; Koval, V.V.; Zharkov, D.O.; Strauss, P.R.; Fedorova, O.S.
Conformational transitions in human AP endonuclease 1 and its active site mutant during abasic site repair
Biochemistry
49
6451-6461
2010
Homo sapiens
Su, D.; Delaplane, S.; Luo, M.; Rempel, D.; Vu, B.; Kelley, M.; Gross, M.; Georgiadis, M.
Interactions of apurinic/apyrimidinic endonuclease with a redox inhibitor: Evidence for an alternate conformation of the enzyme
Biochemistry
50
82-92
2011
Homo sapiens
Kim, W.C.; Berquist, B.R.; Chohan, M.; Uy, C.; Wilson, D.M.; Lee, C.H.
Characterization of the endoribonuclease active site of human apurinic/apyrimidinic endonuclease 1
J. Mol. Biol.
411
960-971
2011
Homo sapiens
Manvilla, B.A.; Pozharski, E.; Toth, E.A.; Drohat, A.C.
Structure of human apurinic/apyrimidinic endonuclease 1 with the essential Mg2+ cofactor
Acta Crystallogr. Sect. D
69
2555-2562
2013
Homo sapiens (P27695), Homo sapiens
Srinivasan, A.; Wang, L.; Cline, C.J.; Xie, Z.; Sobol, R.W.; Xie, X.Q.; Gold, B.
Identification and characterization of human apurinic/apyrimidinic endonuclease-1 inhibitors
Biochemistry
51
6246-6259
2012
Homo sapiens (P27695), Homo sapiens
Adhikari, S.; Manthena, P.V.; Kota, K.K.; Karmahapatra, S.K.; Roy, G.; Saxena, R.; Uren, A.; Roy, R.
A comparative study of recombinant mouse and human apurinic/apyrimidinic endonuclease
Mol. Cell. Biochem.
362
195-201
2012
Homo sapiens (P27695), Homo sapiens, Mus musculus (P28352), Mus musculus
Broxson, C.; Hayner, J.N.; Beckett, J.; Bloom, L.B.; Tornaletti, S.
Human AP endonuclease inefficiently removes abasic sites within G4 structures compared to duplex DNA
Nucleic Acids Res.
42
7708-7719
2014
Homo sapiens
Madlener, S.; Stroebel, T.; Vose, S.; Saydam, O.; Price, B.D.; Demple, B.; Saydam, N.
Essential role for mammalian apurinic/apyrimidinic (AP) endonuclease Ape1/Ref-1 in telomere maintenance
Proc. Natl. Acad. Sci. USA
110
17844-17849
2013
Homo sapiens (P27695), Homo sapiens
Dyrkheeva, N.S.; Lebedeva, N.A.; Lavrik, O.I.
AP endonuclease 1 as a key enzyme in repair of apurinic/apyrimidinic sites
Biochemistry (Moscow)
81
951-967
2016
Homo sapiens (P27695), Homo sapiens, Mus musculus (P28352)
Ilina, E.S.; Khodyreva, S.N.; Lavrik, O.I.
Unusual interaction of human apurinic/apyrimidinic endonuclease 1 (APE1) with abasic sites via the Schiff-base-dependent mechanism
Biochimie
150
88-99
2018
Homo sapiens (P27695), Homo sapiens
Laev, S.S.; Salakhutdinov, N.F.; Lavrik, O.I.
Inhibitors of nuclease and redox activity of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1)
Bioorg. Med. Chem.
25
2531-2544
2017
Homo sapiens (P27695), Homo sapiens (Q9UBZ4), Homo sapiens
Jiang, X.; Shan, J.; Dai, N.; Zhong, Z.; Qing, Y.; Yang, Y.; Zhang, S.; Li, C.; Sui, J.; Ren, T.; Li, M.; Wang, D.
Apurinic/apyrimidinic endonuclease 1 regulates angiogenesis in a transforming growth factor beta-dependent manner in human osteosarcoma
Cancer Sci.
106
1394-1401
2015
Homo sapiens (P27695), Homo sapiens
Guerreiro, P.S.; Estacio, S.G.; Antunes, F.; Fernandes, A.S.; Pinheiro, P.F.; Costa, J.G.; Castro, M.; Miranda, J.P.; Guedes, R.C.; Oliveira, N.G.
Structure-based virtual screening toward the discovery of novel inhibitors of the DNA repair activity of the human apurinic/apyrimidinic endonuclease 1
Chem. Biol. Drug Des.
88
915-925
2016
Homo sapiens (P27695), Homo sapiens
Kotera, N.; Poyer, F.; Granzhan, A.; Teulade-Fichou, M.P.
Efficient inhibition of human AP endonuclease 1 (APE1) via substrate masking by abasic site-binding macrocyclic ligands
Chem. Commun. (Camb.)
51
15948-15951
2015
Homo sapiens (P27695), Homo sapiens
Kladova, O.A.; Bazlekowa-Karaban, M.; Baconnais, S.; Pietrement, O.; Ishchenko, A.A.; Matkarimov, B.T.; Iakovlev, D.A.; Vasenko, A.; Fedorova, O.S.; Le Cam, E.; Tudek, B.; Kuznetsov, N.A.; Saparbaev, M.
The role of the N-terminal domain of human apurinic/apyrimidinic endonuclease 1, APE1, in DNA glycosylase stimulation
DNA Repair
64
10-25
2018
Homo sapiens (P27695), Homo sapiens
Miroshnikova, A.D.; Kuznetsova, A.A.; Vorobjev, Y.N.; Kuznetsov, N.A.; Fedorova, O.S.
Effects of mono- and divalent metal ions on DNA binding and catalysis of human apurinic/apyrimidinic endonuclease 1
Mol. Biosyst.
12
1527-1539
2016
Homo sapiens (P27695), Homo sapiens
Kuznetsov, N.A.; Kupryushkin, M.S.; Abramova, T.V.; Kuznetsova, A.A.; Miroshnikova, A.D.; Stetsenko, D.A.; Pyshnyi, D.V.; Fedorova, O.S.
New oligonucleotide derivatives as unreactive substrate analogues and potential inhibitors of human apurinic/apyrimidinic endonuclease APE1
Mol. Biosyst.
12
67-75
2016
Homo sapiens (P27695), Homo sapiens
Roychoudhury, S.; Nath, S.; Song, H.; Hegde, M.L.; Bellot, L.J.; Mantha, A.K.; Sengupta, S.; Ray, S.; Natarajan, A.; Bhakat, K.K.
Human apurinic/apyrimidinic endonuclease (APE1) is acetylated at DNA damage sites in chromatin, and acetylation modulates its DNA repair activity
Mol. Cell. Biol.
37
e00401-16
2017
Homo sapiens (P27695), Homo sapiens
Kuznetsova, A.A.; Fedorova, O.S.; Kuznetsov, N.A.
Kinetic features of 30-50 exonuclease activity of human AP-endonuclease APE1
Molecules
23
E2101
2018
Homo sapiens (P27695), Homo sapiens
Beaver, J.M.; Lai, Y.; Xu, M.; Casin, A.H.; Laverde, E.E.; Liu, Y.
AP endonuclease 1 prevents trinucleotide repeat expansion via a novel mechanism during base excision repair
Nucleic Acids Res.
43
5948-5960
2015
Homo sapiens (P27695), Homo sapiens
Kuznetsova, A.A.; Matveeva, A.G.; Milov, A.D.; Vorobjev, Y.N.; Dzuba, S.A.; Fedorova, O.S.; Kuznetsov, N.A.
Substrate specificity of human apurinic/apyrimidinic endonuclease APE1 in the nucleotide incision repair pathway
Nucleic Acids Res.
46
11454-11465
2018
Homo sapiens (P27695), Homo sapiens
Batebi, H.; Dragelj, J.; Imhof, P.
Role of AP-endonuclease (Ape1) active site residues in stabilization of the reactant enzyme-DNA complex
Proteins
86
439-453
2018
Homo sapiens (P27695)
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