Information on EC 3.1.4.1 - phosphodiesterase I

New: Word Map on EC 3.1.4.1
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea

EC NUMBER
COMMENTARY
3.1.4.1
-
RECOMMENDED NAME
GeneOntology No.
phosphodiesterase I
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
mechanism
-
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
mechanism, overview
-
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
mode of action
-
-
-
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
the enzyme may be able to recognize nucleoside 5'-monophosphates in the substrates and nick them even if the phosphodiester bonds are closed covalently, although the mode of action of this enzyme on oligo- or polynucleotides is typically exonucleolytic
-
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
ping-pong type mechanism, with participation of a covalent enzyme intermediate
-
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
active site residue is threonine
-
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
enzyme is an exonuclease which needs a free end of an oligonucleotide chain for activity
-
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
PC-1, enzymic activities and regulation of PC-1
-
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
mechanism, transition state
synthetic construct
-
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
catalytic mechanism, the enzyme has a unique catalytic cycle, structure-function analysis overview
Q8BJ37
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
catalytic mechanism, the enzyme has a unique catalytic cycle, structure-function analysis overview
Q4G056
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
catalytic mechanism, the enzyme has a unique catalytic cycle, structure-function analysis overview
E2REL5
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
catalytic mechanism, the enzyme has a unique catalytic cycle, structure-function analysis overview
F1NSQ5
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
catalytic mechanism, the enzyme has a unique catalytic cycle, structure-function analysis overview
Q9VQM4
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
catalytic mechanism, the enzyme has a unique catalytic cycle, structure-function analysis overview. The enzyme's N-terminal catalytic His182 functions as a nucleophile (Hisnuc) to attack the 3'-phospho-tyrosyl linkage. This results in dissociation of the tyrosine (and by extension Topo1) from the DNA end and the formation of a enzyme-DNA covalent reaction intermediate via a 3'-phospho-histidyl linkage
P38319
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
catalytic mechanism, the enzyme has a unique catalytic cycle, structure-function analysis overview. The enzyme's N-terminal catalytic His263 functions as a nucleophile (Hisnuc) to attack the 3'-phospho-tyrosyl linkage. This results in dissociation of the tyrosine (and by extension Topo1) from the DNA end and the formation of a enzyme-DNA covalent reaction intermediate via a 3'-phospho-histidyl linkage
Q9NUW8
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
show the reaction diagram
catalytic mechanism, the enzyme has a unique catalytic cycle, structure-function analysis overview. The enzyme's N-terminal catalytic His182 functions as a nucleophile (Hisnuc) to attack the 3'-phospho-tyrosyl linkage. This results in dissociation of the tyrosine (and by extension Topo1) from the DNA end and the formation of a enzyme-DNA covalent reaction intermediate via a 3'-phospho-histidyl linkage
Saccharomyces cerevisiae ATCC 204508
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoric ester hydrolysis
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
oligonucleotide 5'-nucleotidohydrolase
Hydrolyses both ribonucleotides and deoxyribonucleotides. Has low activity towards polynucleotides. A 3'-phosphate terminus on the substrate inhibits hydrolysis.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5'-exonuclease
-
-
-
-
5'-nucleotide phosphodiesterase
-
-
-
-
5'-phosphodiesterase
-
-
-
-
orthophosphoric diester phosphohydrolase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9025-82-5
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
nutritional regulation of enzyme activity
-
-
Manually annotated by BRENDA team
endonuclease tRNase Z also has phosphodiesterase activity
-
-
Manually annotated by BRENDA team
gene At5g15170 or AtTDP
UniProt
Manually annotated by BRENDA team
Aspergillus batatae
-
-
-
Manually annotated by BRENDA team
Aspergillus fuscus
-
-
-
Manually annotated by BRENDA team
FS-44, 5'-PDase hyperproductive mutant: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
-
-
Manually annotated by BRENDA team
strain ATCC 6633, vegetative and sporulating forms
-
-
Manually annotated by BRENDA team
strain BG581
-
-
Manually annotated by BRENDA team
Bacillus subtilis BG581
strain BG581
-
-
Manually annotated by BRENDA team
var. saccharifera, sugar beet
-
-
Manually annotated by BRENDA team
commercial product
-
-
Manually annotated by BRENDA team
type IV enzyme
-
-
Manually annotated by BRENDA team
gene glaikit or gkt
-
-
Manually annotated by BRENDA team
extremely halophilic bacterium, mixture of 3'- and 5'-exonuclease
-
-
Manually annotated by BRENDA team
fetal, origin of the fetal serum PDEase might be a soluble form of human PC-1, a plasma cell membrane glycoprotein, with a molecular weight of 130000 Da, which possesses alkaline phosphodiesterase I and nucleotide pyrophosphatase activity
-
-
Manually annotated by BRENDA team
gene SMPDL3A
UniProt
Manually annotated by BRENDA team
patients with neurofibromatosis: over-expression of alkaline phosphodiesterase I
-
-
Manually annotated by BRENDA team
patients with uterine cervix neoplasia
-
-
Manually annotated by BRENDA team
PC-1
-
-
Manually annotated by BRENDA team
bifunctional phosphodiesterase/monoesterase
-
-
Manually annotated by BRENDA team
Lactobacillus acidophilus R26
R26
-
-
Manually annotated by BRENDA team
yellow lupin
-
-
Manually annotated by BRENDA team
isozymes NPP1, Npp2, NPP3
-
-
Manually annotated by BRENDA team
8- to 10-week-old C57/BL6 mice
-
-
Manually annotated by BRENDA team
BALB/c; PC-1
-
-
Manually annotated by BRENDA team
DBA/2: liver, spleen, thymus
-
-
Manually annotated by BRENDA team
gene SMPDL3A
UniProt
Manually annotated by BRENDA team
Mus musculus BALB/c
BALB/c
-
-
Manually annotated by BRENDA team
Mus musculus C57/black
gene SMPDL3A
UniProt
Manually annotated by BRENDA team
isozyme NPP1; cv. Nipponbare, isozyme NPP1
UniProt
Manually annotated by BRENDA team
isozyme NPP3; cv. Nipponbare, isozyme NPP3
UniProt
Manually annotated by BRENDA team
native and immobilized on Eupergit C enzyme
-
-
Manually annotated by BRENDA team
; Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
ecto-nucleotide diphosphatase/phosphodiesterase
-
-
Manually annotated by BRENDA team
isoform ecto-nucleotide pyrophosphatase/phosphodiesterase
-
-
Manually annotated by BRENDA team
isozymes PDE1C and PDE1A
-
-
Manually annotated by BRENDA team
PC-1, nucleotide pyrophosphatase/phosphodiesterase I
-
-
Manually annotated by BRENDA team
two isozymes
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
male
-
-
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
UniProt
Manually annotated by BRENDA team
Rhizobium leguminosarum bv. viciae strain 3841
-
-
Manually annotated by BRENDA team
bifunctional phosphodiesterase/phosphomonoesterase
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae ATCC 204508
-
UniProt
Manually annotated by BRENDA team
synthetic construct
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
C8CT07
conservation of the active site motifs typical for all Tdp1 proteins
evolution
Q8BJ37
the enzyme belongs to the phospholipase D, PLD, superfamily, which consists of a highly diverse collection of prokaryotic and eukaryotic enzymes, such as bacterial, plant and mammalian PLDs, cardiolipin and phosphatidylserine synthases, Salmonella typhimurium Nuc and mammalian DNase II endonucleases, restriction enzyme BfiI, poxvirus envelope proteins p37K and K4L, and eukaryotic Tdp1, sequence comparison. Family members show the presence of two histidine-lysine-aspartate-asparagine-HKDN-(HxKx4Dx6N; x being any amino acid) motifs
evolution
Q4G056
the enzyme belongs to the phospholipase D, PLD, superfamily, which consists of a highly diverse collection of prokaryotic and eukaryotic enzymes, such as bacterial, plant and mammalian PLDs, cardiolipin and phosphatidylserine synthases, Salmonella typhimurium Nuc and mammalian DNase II endonucleases, restriction enzyme BfiI, poxvirus envelope proteins p37K and K4L, and eukaryotic Tdp1, sequence comparison. Family members show the presence of two histidine-lysine-aspartate-asparagine-HKDN-(HxKx4Dx6N; x being any amino acid) motifs
evolution
E2REL5
the enzyme belongs to the phospholipase D, PLD, superfamily, which consists of a highly diverse collection of prokaryotic and eukaryotic enzymes, such as bacterial, plant and mammalian PLDs, cardiolipin and phosphatidylserine synthases, Salmonella typhimurium Nuc and mammalian DNase II endonucleases, restriction enzyme BfiI, poxvirus envelope proteins p37K and K4L, and eukaryotic Tdp1, sequence comparison. Family members show the presence of two histidine-lysine-aspartate-asparagine-HKDN-(HxKx4Dx6N; x being any amino acid) motifs
evolution
F1NSQ5
the enzyme belongs to the phospholipase D, PLD, superfamily, which consists of a highly diverse collection of prokaryotic and eukaryotic enzymes, such as bacterial, plant and mammalian PLDs, cardiolipin and phosphatidylserine synthases, Salmonella typhimurium Nuc and mammalian DNase II endonucleases, restriction enzyme BfiI, poxvirus envelope proteins p37K and K4L, and eukaryotic Tdp1, sequence comparison. Family members show the presence of two histidine-lysine-aspartate-asparagine-HKDN-(HxKx4Dx6N; x being any amino acid) motifs
evolution
Q9VQM4
the enzyme belongs to the phospholipase D, PLD, superfamily, which consists of a highly diverse collection of prokaryotic and eukaryotic enzymes, such as bacterial, plant and mammalian PLDs, cardiolipin and phosphatidylserine synthases, Salmonella typhimurium Nuc and mammalian DNase II endonucleases, restriction enzyme BfiI, poxvirus envelope proteins p37K and K4L, and eukaryotic Tdp1, sequence comparison. Family members show the presence of two histidine-lysine-aspartate-asparagine-HKDN-(HxKx4Dx6N; x being any amino acid) motifs
evolution
Q9NUW8
the enzyme belongs to the phospholipase D, PLD, superfamily, which consists of a highly diverse collection of prokaryotic and eukaryotic enzymes, such as bacterial, plant and mammalian PLDs, cardiolipin and phosphatidylserine synthases, Salmonella typhimurium Nuc and mammalian DNase II endonucleases, restriction enzyme BfiI, poxvirus envelope proteins p37K and K4L, and eukaryotic Tdp1, sequence comparison. Family members show the presence of two histidine-lysine-aspartate-asparagine-HKDN-(HxKx4Dx6N; x being any amino acid) motifs, three-dimensional structural comparison of four PLD superfamily members, overview
evolution
P38319
the enzyme belongs to the phospholipase D, PLD, superfamily, which consists of a highly diverse collection of prokaryotic and eukaryotic enzymes, such as bacterial, plant and mammalian PLDs, cardiolipin and phosphatidylserine synthases, Salmonella typhimurium Nuc and mammalian DNase II endonucleases, restriction enzyme BfiI, poxvirus envelope proteins p37K and K4L, and eukaryotic Tdp1, sequence comparison. Family members show the presence of two histidine-lysine-aspartate-asparagine-HKDN-(HxKx4Dx6N; x being any amino acid) motifs, three-dimensional structural comparison of PLD superfamily members, overview
evolution
Q92484
the enzyme is a member of the metallophosphoesterase enzyme family, the molecular mass of secreted SMPDL3A is tissue and/or species dependent
evolution
P70158
the enzyme is a member of the metallophosphoesterase enzyme family, the molecular mass of secreted SMPDL3A is tissue and/or species dependent
evolution
-
the enzyme is a member of the phospholipase D superfamily of enzymes that catalyze the hydrolysis of a variety of phosphodiester bonds in many different substrates
evolution
-
the enzyme is phylogenetically conserved
evolution
-
the enzymes belongs to the ectonucleotide pyrophosphatase/phosphodiesterase (NPP) family
evolution
-
tyrosyl-DNA phosphodiesterase I is a member of the phospholipase D superfamily of enzymes
evolution
Mus musculus C57/black
-
the enzyme is a member of the metallophosphoesterase enzyme family, the molecular mass of secreted SMPDL3A is tissue and/or species dependent
-
evolution
Saccharomyces cerevisiae ATCC 204508
-
the enzyme belongs to the phospholipase D, PLD, superfamily, which consists of a highly diverse collection of prokaryotic and eukaryotic enzymes, such as bacterial, plant and mammalian PLDs, cardiolipin and phosphatidylserine synthases, Salmonella typhimurium Nuc and mammalian DNase II endonucleases, restriction enzyme BfiI, poxvirus envelope proteins p37K and K4L, and eukaryotic Tdp1, sequence comparison. Family members show the presence of two histidine-lysine-aspartate-asparagine-HKDN-(HxKx4Dx6N; x being any amino acid) motifs, three-dimensional structural comparison of PLD superfamily members, overview
-
malfunction
-
PC-1 is the major source of the elevated phosphate levels in chondrocytes and fibroblasts of patients with familial calcium pyrophosphate dehydrate deposition disease, CPPD. CPPD crystals may be a hallmark of the pathology of osteoarthritis
malfunction
-
Pde1c-/- and Pde4a-/- knockout mutants to examine the role of the PDEs in olfactory transduction. Pde1c-/- OSNs (olfactory sensory neuron cilia) show reduced sensitivity and attenuated adaptation to repeated stimulation, suggesting that PDE1C may be involved in regulating sensitivity and adaptation
malfunction
Q8H1D9
a loss-of-function AtTDP mutation displays developmental defects and dwarf phenotype in Arabidopsis. This phenotype is substantially caused by decreased cell numbers without any change of individual cell sizes. The tdp plants exhibit hypersensitivities to camptothecin, a potent topoisomerase I inhibitor, and show rigorous cell death in cotyledons and rosette leaves, suggesting the failure of DNA damage repair in tdp mutants
malfunction
-
mutations of the Tdp1 gene are involved in the disease spinocerebellar ataxia with axonal neuropathy
malfunction
-
phosphodiesterase-1 inhibition decreases vascular contraction in arteries from angiotensin II hypertensive, but not control, rats
malfunction
-
aberrant nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) activity is associated with chondrocalcinosis, osteoarthritis, and type 2 diabetes
malfunction
P38319
deletion of the enzyme in budding yeast leads to an increase in Topo1-dependent cytotoxicity either induced by expression of the toxic Topo1T722A mutant enzyme or cells treated with camptothecin
malfunction
Q8BJ37
Tdp1-/- enzyme knockout mice do not show increased sensitivity to etoposide, i.e. VP16
malfunction
-
Tdp1-knock-out Gallus gallus DT40 cells are hypersensitive to camptothecin and bleomycin but also to etoposide, methyl methanesulfonate, H2O2, and ionizing radiation and they are deficient in mitochondrial enzyme activity, phenotype, overview
malfunction
-
the c03958 insertion gene gkt disruption mutant of TDP1 is generally healthy and fertile, but females exhibit reduced lifespan and diminished climbing ability. Insertion mutant c03958 larvae are exposed to bleomycin, an agent that produces oxidative DNA damage, or topoisomerase I-targeted drugs (camptothecin and a noncamptothecin indenoisoquinoline derivative, LMP-776), survivors display rough eye patches, which are rescued by neuronal expression of wild-type enzyme TDP1, overview
malfunction
Q9NUW8
the mutation H493R forms the molecular basis for the autosomal recessive neurodegenerative disease spinocerebellar ataxia with axonal neuropathy, SCAN1, and results in an increased stability of its Tdp1-DNA reaction intermediate, overview. Enzyme inhibition might potentiate camptothecin-based chemotherapy, overview
malfunction
-
whilst the enzyme mutants H493R (SCAN1) and H263A retain the ability to bind an apurinic/apyrimidinic site-containing DNA, both mutants do not reveal endonuclease activity
malfunction
Saccharomyces cerevisiae ATCC 204508
-
deletion of the enzyme in budding yeast leads to an increase in Topo1-dependent cytotoxicity either induced by expression of the toxic Topo1T722A mutant enzyme or cells treated with camptothecin
-
metabolism
Q924C3
(R,S)-isoproterenol decreases the amount of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 protein by 75% and 81%, respectively. Contrary to downregulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1, an upregulation of glial fibrillary acidic protein, a differentiation marker for astrocytic cells is observed. Ca2+, PKA, PI 3-K/PKB/GSK-3, Epac/Rap1/PP2A and MAP kinase modules are not involved in the inhibition of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene expression, overview
metabolism
-
TDP1 knockdown does not produce a change in sensitivity to camptothecin, whereas co-silencing of other pathways cooperating with TDP1 in cell response to topoisomerase I poisons indicates that XRCC1 and BRCA1 are major regulators of sensitivity
metabolism
-
the tyrosyl-DNA phosphodiesterase I hydrolyzes the phosphotyrosyl linkage between degraded Top1 and DNA, then polynucleotide kinase phosphatase hydrolyzes the resulting 3'-phosphate end and catalyzes the phosphorylation of the 5'-hydroxyl end of the broken DNA strand. This results in a broken DNA strand with termini consisting of a 5'-phosphate and 3'-hydroxyl for DNA repair. DNA polymerase beta replaces the missing DNA segment, and finally DNA ligase III reseals the broken DNA. Tyrosyl-DNA phosphodiesterase I is the only enzyme that specifically catalyzes the hydrolysis of the phosphodiester bond between the catalytic Tyr723 of Top1 and DNA-3'-phosphate
physiological function
-
PC-1 is an enzymatic generator of diphosphate and a critical regulator of tissue mineralization
physiological function
Q8H1D9
AtTDP plays a clear role in the repair of topoisomerase I-DNA complexes in Arabidopsis, the tyrosyl-DNA phosphodiesterase 1 is a key enzyme that hydrolyzes the phosphodiester bond between tyrosine of topoisomerase and 3'-phosphate of DNA and repairs topoisomerase-mediated DNA damage during chromosome metabolism. Recombinant AtTDP protein certainly hydrolyzes the 3'-phosphotyrosyl DNA substrates related to repairing in vivo topoisomerase I-DNA-induced damage
physiological function
-
phosphodiesterase 1 plays a role in decreased cGMP level contributing to increased contraction in arteries from hypertensive rats. Ang II augments PDE1 activation, decreasing the bioavailability of cyclic guanosine 3',5'-monophosphate, and contributing to increased vascular contractility, effects of different PDF isozymes, overview
physiological function
-
role and underlying mechanism of cyclic nucleotide phosphodiesterase 1, PDE1, in regulating collagen I in synthetic vascular smooth muscle cells, overview
physiological function
-
role of Tdp1 in the new APE-independent base excision repair pathway in mammals
physiological function
C8CT07
th enzyme participates in topoisomerase I-mediated DNA damage repair process and thereby counteracts the cytotoxic effect of topoisomerase I inhibitors
physiological function
-
tyrosyl-DNA phosphodiesterase 1 catalyses the hydrolysis of phosphodiester linkages between a DNA 3' phosphate and a tyrosine residue as well as a variety of other DNA 3 substituents, and is implicated in the repair of covalent complexes involving eukaryotic type IB topoisomerases. Processing by the proteasome is required for TDP1 cleavage in vivo
physiological function
-
tyrosyl-DNA phosphodiesterase 1 is a key enzyme that hydrolyzes the phosphodiester bond between tyrosine of topoisomerase and 3'-phosphate of DNA and repairs topoisomerase-mediated DNA damage during chromosome metabolism
physiological function
-
tyrosyl-DNA phosphodiesterase 1 is an enzyme vital to the repair of covalent DNA-topoisomerase adducts, e.g. induced by the mycotoxin alternariol, it affects alternariol-mediated genotoxicity. TDP1 plays an important role in the repair of topoisomerase-mediated DNA damage. The repair enzyme TDP1 is a factor for the modulation of AOH-mediated DNA damage in human cells. TDP1 is also involved in the repair of topoisomerase II-induced DNA damage
physiological function
-
tyrosyl-DNA phosphodiesterase 1 plays a unique function as it catalyzes the repair of topoisomerase I-mediated DNA damage. TDP1 alone can account for mild levels of camptothecin resistance, repair of topoisomerase I-mediated DNA damage likely occurs through redundant pathways mainly implicating BRCA1 and XRCC1, but not RAD17 and PARP1
physiological function
-
human tyrosyl-DNA phosphodiesterase 1 catalyzes the apurinic/apyrimidinic site cleavage reaction to generate breaks with the 3'- and 5'-phosphate termini. The enzyme activity can contribute to the repair of apurinic/apyrimidinic sites particularly in DNA structures containing ssDNA region or apurinic/apyrimidinic sites in the context of clustered DNA lesions
physiological function
Q92484
SMPDL3A is the major nucleotide phosphodiesterase secreted by human THP-1 macrophages after LXR stimulation, it may play a novel role in the pathobiology of atherosclerosis. SMPDL3A is a major source of nucleotide phosphodiesterase activity secreted by LXR-stimulated human macrophages, enzyme expression and secretion is regulated by intracellular cAMP, and is regulated by liver X receptor, LXR,. The CREs in the promoter region of SMPDL3A may play a functional role in primary human macrophages. The enzyme is capable of hydrolyzing sphingomyelin in oxidized LDL particles, transforming them into a more aggregation prone form which is more readily retained by arterial proteoglycans. But SMPDL3A is not an acid sphingomyelinase, but unexpectedly is active against nucleotide diphosphate and triphosphate substrates at acidic and neutral pH
physiological function
-
the enzyme is critical for neuroprotection, normal longevity, and repair of damaged DNA through the removal of blocking lesions at the 3'-ends of DNA or RNA
physiological function
-
the enzyme plays a critical role in the cellular repair of topoisomerase 1-mediated DNA damage
physiological function
-
the enzyme plays a key role in the repair of damaged DNA resulting from the topoisomerase I inhibitor camptothecin and a variety of other DNA-damaging anticancer agents
physiological function
-
tyrosyl-DNA phosphodiesterase 1 repairs topoisomerase I cleavage complexes by hydrolyzing their 3'-phosphotyrosyl DNA bonds and repairs bleomycin-induced DNA damage by hydrolyzing 3'-phosphoglycolates
physiological function
-
tyrosyl-DNA phosphodiesterase 1 repairs topoisomerase I cleavage complexes by hydrolyzing their 3'-phosphotyrosyl DNA bonds and repairs bleomycin-induced DNA damage by hydrolyzing 3'-phosphoglycolates. The yeast enzyme is also implicated in the repair of topoisomerase II-DNA cleavage complexes. The enzyme and CtIP act in parallel pathways for the repair of topoisomerase I cleavage complexes and methyl methanesulfonate-induced lesions but are epistatic for topoisomerase II cleavage complexes
physiological function
Q4G056
tyrosyl-DNA phosphodiesterase I is a eukaryotic DNA repair enzyme that catalyzes the removal of covalent 3'-DNA adducts, the enzyme hydrolyzes the 3'-phospho-tyrosyl that in the cell covalently links DNA topoisomerase I and DNA
physiological function
E2REL5
tyrosyl-DNA phosphodiesterase I is a eukaryotic DNA repair enzyme that catalyzes the removal of covalent 3'-DNA adducts, the enzyme hydrolyzes the 3'-phospho-tyrosyl that in the cell covalently links DNA topoisomerase I and DNA
physiological function
F1NSQ5
tyrosyl-DNA phosphodiesterase I is a eukaryotic DNA repair enzyme that catalyzes the removal of covalent 3'-DNA adducts, the enzyme hydrolyzes the 3'-phospho-tyrosyl that in the cell covalently links DNA topoisomerase I and DNA
physiological function
Q9VQM4
tyrosyl-DNA phosphodiesterase I is a eukaryotic DNA repair enzyme that catalyzes the removal of covalent 3'-DNA adducts, the enzyme hydrolyzes the 3'-phospho-tyrosyl that in the cell covalently links DNA topoisomerase I and DNA
physiological function
Q9NUW8
tyrosyl-DNA phosphodiesterase I is a eukaryotic DNA repair enzyme that catalyzes the removal of covalent 3'-DNA adducts, the enzyme hydrolyzes the 3'-phospho-tyrosyl that in the cell covalently links DNA topoisomerase I and DNA. Phosphorylation of Ser81 regulates hTdp1 targeting to sites of DNA damage and stabilizes its interaction with X-ray repair cross-complementing protein 1 (XRCC1) and/or DNA ligase III similar to how ATM-mediated phosphorylation of PNKP promotes its activity at DNA lesions. The human enzyme expressed in DT40 chicken B-lymphoblast cells plays a protective role against etoposide
physiological function
P38319
tyrosyl-DNA phosphodiesterase I is a eukaryotic DNA repair enzyme that catalyzes the removal of covalent 3'-DNA adducts, the enzyme hydrolyzes the 3'-phospho-tyrosyl that in the cell covalently links DNA topoisomerase I and DNA. The enzyme may play a role in chemo-resistance to pharmacologic inhibitors of topoisomerase I
physiological function
Q8BJ37
tyrosyl-DNA phosphodiesterase I is a eukaryotic DNA repair enzyme that catalyzes the removal of covalent 3'-DNA adducts, the enzyme hydrolyzes the 3'-phospho-tyrosyl that in the cell covalently links DNA topoisomerase I and DNA. The enzyme plays a role in suppressing etoposide-induced DNA damage
physiological function
Rattus norvegicus Sprague-Dawley
-
phosphodiesterase 1 plays a role in decreased cGMP level contributing to increased contraction in arteries from hypertensive rats. Ang II augments PDE1 activation, decreasing the bioavailability of cyclic guanosine 3',5'-monophosphate, and contributing to increased vascular contractility, effects of different PDF isozymes, overview
-
physiological function
Saccharomyces cerevisiae ATCC 204508
-
tyrosyl-DNA phosphodiesterase I is a eukaryotic DNA repair enzyme that catalyzes the removal of covalent 3'-DNA adducts, the enzyme hydrolyzes the 3'-phospho-tyrosyl that in the cell covalently links DNA topoisomerase I and DNA. The enzyme may play a role in chemo-resistance to pharmacologic inhibitors of topoisomerase I
-
metabolism
Rattus norvegicus Wistar
-
(R,S)-isoproterenol decreases the amount of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 protein by 75% and 81%, respectively. Contrary to downregulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1, an upregulation of glial fibrillary acidic protein, a differentiation marker for astrocytic cells is observed. Ca2+, PKA, PI 3-K/PKB/GSK-3, Epac/Rap1/PP2A and MAP kinase modules are not involved in the inhibition of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene expression, overview
-
additional information
-
knockdown of the enzyme TDP1 in U2-OS cells does not increase sensitivity to gimatecan
additional information
C8CT07
overexpression of the active enzyme protects the parasites against topoisomerase IB inhibitor camptothecin and oxidative agent H2O2-mediated cytotoxicity and its downregulation rendered the parasites hypersensitive to camptothecin. Downregulation of LdTdp1 mRNA occurs because of blockage of transcription rather than increased turnover, transcriptional regulation, overview
additional information
-
Tdp1 is known to interact stably with BER proteins: DNA polymerase beta, XRCC1, PARP1 and DNA ligase III
additional information
Q92484
expression and sequence comparisons, overview
additional information
P70158
expression and sequence comparisons, overview
additional information
-
the enzyme is composed of two domains related by a pseudo-twofold axis of symmetry. Each domain contributes a histidine and a lysine residue to form an active site that is centrally located at the symmetry axis. Four additional residues N283, Q294, N516, and E538 are also positioned near the active site
additional information
Mus musculus C57/black
-
expression and sequence comparisons, overview
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
10-hydroxydecyl-oligonucleotide + H2O
?
show the reaction diagram
-
different sequences of the oligonucleotides, overview. The enzyme catalyzes the cleavage of the synthetic analogue of the apurinic/apyrimidinic site
-
-
?
2-hydroxypropyl-p-nitrophenyl phosphate + H2O
2-hydroxypropyl-p-nitrophenol + phosphate
show the reaction diagram
synthetic construct
-
-
-
?
2-naphthyl chloromethylphosphonate + H2O
2-naphthol + chloromethylphosphonic acid
show the reaction diagram
-
-
-
-
?
2-naphthyl methylphosphonate + H2O
2-naphthol + methylphosphonic acid
show the reaction diagram
-
-
-
-
?
2-naphthyl phenylphosphonate + H2O
2-naphthol + benzenephosphonic acid
show the reaction diagram
-
-
-
-
?
3'-O-acetyl-5'-O-[hydroxy(4-nitrophenoxy)phosphoryl]thymidine + H2O
p-nitrophenol + 3'-O-acetylthymidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
3'-p-nitrophenylthymidine 3'-phosphate + H2O
3'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
3'-phosphoadenosine 5'-phosphosulfate + H2O
?
show the reaction diagram
-
-
-
-
?
3-hydroxy-2(hydroxymethyl)-tetrahydrofuran-oligonucleotide + H2O
?
show the reaction diagram
-
different sequences of the oligonucleotides, overview. The enzyme catalyzes the cleavage of the synthetic analogue of the apurinic/apyrimidinic site. In the case of tetrahydrofuran, the enzyme generates break with the 5'-tetrahydrofuran and the 3'-phosphate termini
the enzyme generates a non-phosphorylated 5'-THF-terminus by the cleavage of 3-hydroxy-2(hydroxymethyl)-tetrahydrofuran-containing DNA
-
?
4-methylumbelliferyl phenylphosphonate + H2O
4-methylumbelliferone + phenylphosphonic acid
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl thymidine 5'-phosphate + H2O
4-methylumbelliferone + 5'-TMP
show the reaction diagram
-
-
-
-
?
4-nitrophenyl phenyl phosphonate + H2O
4-nitrophenol + phenyl phosphonate
show the reaction diagram
-
-
-
-
?
4-nitrophenyl phosphate + H2O
4-nitrophenol + phosphate
show the reaction diagram
-
-
-
-
?
4-nitrophenyl phosphocholine + H2O
4-nitrophenol + phosphocholine
show the reaction diagram
Q92484
secreted recombinant human SMPDL3A hydrolyzes 4-nitrophenyl phosphorylcholine, a synthetic analogue of the phosphorylcholine headgroup of lipids such as sphingomyelin and phosphatidylcholine
-
-
?
4-nitrophenyl phosphorothioate + H2O
?
show the reaction diagram
-
-
-
-
?
4-nitrophenyl sulfate + H2O
?
show the reaction diagram
-
-
-
-
?
5'-p-nitrophenyl deoxythymidine 5'-phosphate + H2O
5'-dTMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
5'-p-nitrophenyl deoxythymidine 5'-phosphate + H2O
5'-dTMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
5'-p-nitrophenyl deoxythymidine 5'-phosphate + H2O
5'-dTMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
5'-p-nitrophenyl deoxythymidine 5'-phosphate + H2O
5'-dTMP + p-nitrophenol
show the reaction diagram
-
nucleotide pyrophosphatase/phosphodiesterase I
-
-
?
5'-p-nitrophenyl-2',3'-isopropyl-5'-UMP + H2O
?
show the reaction diagram
-
-
-
-
?
5'-p-nitrophenyladenosine 5'-phosphate + H2O
5'-AMP + p-nitrophenol
show the reaction diagram
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
-
-
?
5'-p-nitrophenylnucleoside 5'-monophosphate + H2O
nucleoside 5'-monophosphate + p-nitrophenol
show the reaction diagram
-
-
-
-
?
5'-p-nitrophenylnucleoside 5'-monophosphate + H2O
nucleoside 5'-monophosphate + p-nitrophenol
show the reaction diagram
-
-
-
?
5'-p-nitrophenylnucleoside 5'-monophosphate + H2O
nucleoside 5'-monophosphate + p-nitrophenol
show the reaction diagram
-
-
-
?
5'-p-nitrophenylnucleoside 5'-monophosphate + H2O
nucleoside 5'-monophosphate + p-nitrophenol
show the reaction diagram
-
-
-
-
?
5'-p-nitrophenyluridine 5'-phosphate + H2O
5'-UMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
5'-p-nitrophenyluridine 5'-phosphate + H2O
5'-UMP + p-nitrophenol
show the reaction diagram
-
70% as fast as 5'-p-nitrophenylthymidine 5'-phosphate
-
-
?
adenosine 5'-P1-tetraphospho-P4-5'''-adenosine + H2O
AMP + ATP
show the reaction diagram
-
-
-
?
adenosine 5'-P1-tetraphospho-P4-5'''-adenosine + H2O
AMP + ATP
show the reaction diagram
-
-
-
-
?
adenosine 5'-P1-tetraphospho-P4-5'''-adenosine + H2O
AMP + ATP
show the reaction diagram
-
-
-
?
adenosine 5'-P1-tetraphospho-P4-5'''-adenosine + H2O
AMP + ATP
show the reaction diagram
-
-
-
-
?
adenosine 5'-P1-tetraphospho-P4-5'''-guanosine + H2O
?
show the reaction diagram
-
-
-
-
?
adenosine 5'-phosphosulfate + H2O
?
show the reaction diagram
-
-
-
-
?
adenosyl uridine 5'-phosphate + H2O
5'-UMP + adenosine
show the reaction diagram
-
-
-
?
adenylyl-2',5'-adenosine + H2O
?
show the reaction diagram
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
-
-
?
adenylyl-3',5'-adenosine + H2O
adenosine + 5'-AMP
show the reaction diagram
-
-
-
?
adenylyl-3',5'-adenosine + H2O
adenosine + 5'-AMP
show the reaction diagram
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
-
-
?
adenylyl-3',5'-cytidine + H2O
adenosine 3'-phosphate + cytidine
show the reaction diagram
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
-
-
?
adenylyl-3',5'-uridine + H2O
?
show the reaction diagram
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
-
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
-
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
-
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
-
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
slowly
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
slowly
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
PC-1
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
PC-1
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
pyrophosphatase activity
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
ADPase activity, hydrolysis of ADP by human plasma PDEase acts as an inhibitor of platelet aggregation
-
?
ADP-ribose + H2O
5'-AMP + ribosyl monophosphate
show the reaction diagram
-
-
-
?
ADP-ribose + H2O
?
show the reaction diagram
-
-
-
?
ApA + H2O
5'-AMP + adenosine
show the reaction diagram
-
-
-
-
?
ApA + H2O
5'-AMP + adenosine
show the reaction diagram
-
-
-
?
ApC + H2O
5'-CMP + adenosine
show the reaction diagram
-
-
-
?
ApG + H2O
5'-GMP + adenosine
show the reaction diagram
-
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
slowly
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
slowly
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
PC-1
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
PC-1
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
PC-1
PC-1
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
pyrophosphatase activity
-
-
?
ATP + H2O
5'-AMP + diphosphate
show the reaction diagram
-
calf
-
?
ATP + H2O
AMP + diphosphate
show the reaction diagram
-
-
-
-
?
bis(4-methylumbelliferyl) phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis(4-nitrophenyl) phosphate + H2O
4-nitrophenyl phosphate + 4-nitrophenol
show the reaction diagram
-
-
-
-
?
bis(4-nitrophenyl)phosphate + H2O
4-nitrophenyl phosphate + 4-nitrophenol
show the reaction diagram
-
-
-
-
?
bis(p-nitrophenyl) phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis(p-nitrophenyl) phosphate + H2O
?
show the reaction diagram
-
-
-
-
-
bis(p-nitrophenyl) phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis(p-nitrophenyl) phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis(p-nitrophenyl) phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis(p-nitrophenyl) phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis(p-nitrophenyl) phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis(p-nitrophenyl) phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis(p-nitrophenyl) phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis-4-nitrophenyl phosphate + H2O
4-nitrophenol + 4-nitrophenyl phosphate
show the reaction diagram
-
-
-
-
?
bis-ethylene glycolyl-oligonucleotide + H2O
?
show the reaction diagram
-
different sequences of the oligonucleotides, overview. The enzyme catalyzes the cleavage of the synthetic analogue of the apurinic/apyrimidinic site
-
-
?
bis-p-nitrophenyl phosphate + H2O
p-nitrophenol + phosphate
show the reaction diagram
-
-
processive two-step mechanism
-
?
bis-p-nitrophenyl phosphate + H2O
p-nitrophenol + p-nitrophenyl phosphate
show the reaction diagram
-
-
-
?
bis-p-nitrophenyl phosphate + H2O
p-nitrophenol + p-nitrophenyl phosphate
show the reaction diagram
Q58346
-
-
-
-
bis-p-nitrophenyl phosphate + H2O
p-nitrophenol + p-nitrophenyl phosphate
show the reaction diagram
P37049, P39300, P67095
-
-
-
-
bis-p-nitrophenyl phosphate + H2O
p-nitrophenyl phosphate + nitrophenol
show the reaction diagram
-
-
-
-
?
bis-p-nitrophenyl phosphate + H2O
p-nitrophenyl phosphate + nitrophenol
show the reaction diagram
-
-
-
-
?
cAMP + H2O
?
show the reaction diagram
-
-
-
-
-
cAMP + H2O
?
show the reaction diagram
-
incubated with or without 0.2 mM CaCl2, 10 mU calmodulin, and PDE1 inhibitor vinpocetin, 30C, pH 7.5
-
-
?
CDP-choline + H2O
?
show the reaction diagram
-
-
-
-
?
CpU + H2O
5'-UMP + cytidine
show the reaction diagram
-
-
-
?
cyclic 3',5'-mononucleotides + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
slowly
-
?
cyclic 3',5'-mononucleotides + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
PC-1
-
-
?
cyclic 3',5'-mononucleotides + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
PC-1
-
-
?
cyclic 3',5'-mononucleotides + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
3',5'-cAMP, slowly
-
-
?
cyclic 3',5'-mononucleotides + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
cyclic AMP: not a substrate
-
-
-
cyclic 3',5'-mononucleotides + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
phosphodiester bonds
-
-
?
cyclic 3',5'-mononucleotides + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
phosphodiester bonds
-
?
cyclic 3',5'-mononucleotides + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
phosphodiester bonds
-
-
?
cyclic 3',5'-mononucleotides + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
PDE1 inhibitory activity assays
-
-
?
cytidylyl-3',5'-adenosine + H2O
?
show the reaction diagram
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
-
-
?
diadenosine 5',5'''-P1,P3-triphosphate + H2O
AMP + ADP
show the reaction diagram
-
-
-
?
diadenosine 5',5'''-P1,P3-triphosphate + H2O
AMP + ADP
show the reaction diagram
-
-
-
-
-
diadenosine 5',5'''-P1,P3-triphosphate + H2O
AMP + ADP
show the reaction diagram
-
-
-
?
diadenosine diphosphate + H2O
?
show the reaction diagram
-
-
-
-
?
diadenosine polyphosphate + H2O
AMP + adenosine polyphosphate-1
show the reaction diagram
-
-
-
?
diadenosine polyphosphate + H2O
AMP
show the reaction diagram
-
phosphodiesterase can be considered as a catabolic enzyme
-
-
-
diadenosine polyphosphate + H2O
AMP
show the reaction diagram
-
phosphodiesterase can be considered as a catabolic enzyme
-
?
diethenoadenosine polyphosphate + H2O
ethenoadenosine 5'-monophosphate + ethenoadenosine (n-1)5'-polyphosphate
show the reaction diagram
-
-
-
-
?
dinucleoside monophosphates + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
dinucleoside monophosphates + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
dinucleoside monophosphates + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
dinucleoside monophosphates + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
3'-5' linkage
-
?
dinucleoside monophosphates + H2O
mononucleoside 5'-phosphate
show the reaction diagram
-
3'-5' linkage, no specificity toward bases or sugars, 2'-5' linkage
-
-
?
dinucleoside polyphosphate + H2O
?
show the reaction diagram
-
-
-
-
?
dinucleoside polyphosphate + H2O
?
show the reaction diagram
-
-
-
-
?
dinucleoside tetraphosphate + H2O
?
show the reaction diagram
-
-
-
-
?
dinucleotides + H2O
?
show the reaction diagram
-
-
-
-
?
dinucleotides + H2O
?
show the reaction diagram
-
-
-
-
?
dinucleotides + H2O
?
show the reaction diagram
-
3'-hydroxyl-terminated 3'-5'and 2'-5' linkage without specificity toward bases or sugars
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
P06802
-
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
PC-1
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
PC-1
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
enzyme hydolyzes single-stranded DNA more preferentially than double-stranded DNA, the enzyme also hydrolyzes nicked superhelical covalently closed circular phiX174RFI DNA to yield first open circular DNA and then linear DNA
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
native and denatured DNA
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
immobilized enzyme: not a substrate
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
heat-denatured: very slowly, native DNA is not hydrolyzed
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
enzyme hydrolyzes single-stranded DNA, no activity with double-stranded DNA
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
enzyme hydrolyzes single-stranded DNA, no activity with double-stranded DNA
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
enzyme hydrolyzes single-stranded DNA, no activity with double-stranded DNA
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
denatured DNA. Native DNA is resistant
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
denatured DNA. Native DNA is resistant
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
denatured DNA. Native DNA is resistant
-
-
?
downstream cleavage product-RNA + H2O
?
show the reaction diagram
-
-
-
-
?
FAD + H2O
AMP + FMN
show the reaction diagram
-
-
-
?
GDP-mannose + H2O
?
show the reaction diagram
-
-
-
-
?
GTP + H2O
?
show the reaction diagram
-
-
-
-
?
guanylyl-3',5'-adenosine + H2O
?
show the reaction diagram
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
-
-
?
NAD+ + H2O
5'-AMP + NMN
show the reaction diagram
-
-
-
?
NAD+ + H2O
5'-AMP + NMN
show the reaction diagram
-
-
-
?
NAD+ + H2O
5'-AMP + NMN
show the reaction diagram
-
-
-
-
?
NAD+ + H2O
5'-AMP + NMN
show the reaction diagram
-
-
-
?
NAD+ + H2O
5'-AMP + NMN
show the reaction diagram
-
-
-
-
?
NAD+ + H2O
5'-AMP + NMN
show the reaction diagram
-
-
-
-
?
NAD+ + H2O
5'-AMP + NMN
show the reaction diagram
-
-
-
?
NAD+ + H2O
5'-AMP + NMN
show the reaction diagram
-
slowly
-
-
?
NAD+ + H2O
5'-AMP + NMN
show the reaction diagram
-
pyrophosphatase activity
-
?
NAD+ + H2O
5'-AMP + NMN
show the reaction diagram
-
pyrophosphatase activity
-
-
?
NAD+ + H2O
5'-AMP + NMN
show the reaction diagram
-
calf
-
?
NADP+ + H2O
NAD+ + phosphate
show the reaction diagram
-
-
-
-
?
NADP+ + H2O
NAD+ + phosphate
show the reaction diagram
-
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
-
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
-
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
-
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
PC-1
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
PC-1
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
Lactobacillus acidophilus R26
-
-
-
?
p-nitrophenyl 5'-thymidine monophosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
Q58346
-
-
-
-
p-nitrophenyl 5'-thymidine monophosphate + H2O
p-nitrophenol + 5'-thymidine monophosphate
show the reaction diagram
-
-
-
-
?
p-nitrophenyl 5'-thymidine monophosphate + H2O
p-nitrophenol + 5'-thymidine monophosphate
show the reaction diagram
P37049, P39300, P67095
-
-
-
-
p-nitrophenyl chloromethylphosphonate + H2O
p-nitrophenol + chloromethylphosphonic acid
show the reaction diagram
-
-
-
-
?
p-nitrophenyl ethyl phosphate + H2O
p-nitrophenol + ethyl hydrogen phosphate
show the reaction diagram
-
-
-
-
?
p-nitrophenyl methylphosphonate + H2O
p-nitrophenol + methylphosphonic acid
show the reaction diagram
-
-
-
-
?
p-nitrophenyl phenylphosphonate + H2O
p-nitrophenol + benzenephosphonic acid
show the reaction diagram
-
-
-
-
?
p-nitrophenyl phenylphosphonate + H2O
p-nitrophenol + benzenephosphonic acid
show the reaction diagram
-
-
-
-
?
p-nitrophenyl phenylphosphonate + H2O
p-nitrophenol + benzenephosphonic acid
show the reaction diagram
-
-
-
-
?
p-nitrophenyl phenylphosphonate + H2O
p-nitrophenol + benzenephosphonic acid
show the reaction diagram
-
-
-
-
?
p-nitrophenyl phenylphosphonate + H2O
p-nitrophenol + phenylphosphonic acid
show the reaction diagram
-
-
-
-
?
p-nitrophenylphosphorylcholine + H2O
p-nitrophenol + phosphorylcholine
show the reaction diagram
Q58346
-
-
-
-
p-nitrophenylphosphorylcholine + H2O
p-nitrophenol + phosphorylcholine
show the reaction diagram
P37049, P39300, P67095
-
-
-
-
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
-
PC-1
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
show the reaction diagram
Lactobacillus acidophilus R26
-
-
-
-
?
P1,P4-bis(5'-uridyl) tetraphosphate + H2O
UMP + uridine 5'-triphosphate
show the reaction diagram
-
-
-
?
phosphonate ester + H2O
?
show the reaction diagram
-
-
-
-
?
poly A + H2O
5'-AMP
show the reaction diagram
-
-
-
?
poly A + H2O
5'-AMP
show the reaction diagram
-
-
-
?
poly A + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
poly C + H2O
5'-CMP
show the reaction diagram
-
-
-
?
poly C + H2O
5'-CMP
show the reaction diagram
-
-
-
-
?
poly d(A-T)2 + H2O
?
show the reaction diagram
-
-
-
-
?
poly G + H2O
5'-GMP
show the reaction diagram
-
-
-
?
poly U + H2O
5'-UMP
show the reaction diagram
-
-
-
?
poly U + H2O
5'-UMP
show the reaction diagram
-
-
-
?
poly U + H2O
5'-UMP
show the reaction diagram
-
-
-
-
?
poly(I) + H2O
5'-IMP
show the reaction diagram
-
-
-
?
poly(I) + H2O
5'-IMP
show the reaction diagram
-
slowly
-
-
?
polymer synthesized from NAD+ + H2O
?
show the reaction diagram
-
chain length 27-30
-
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
-
-
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
-
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
very slowly
-
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
-
-
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
-
-
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
-
-
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
-
-
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
PC-1
-
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
-
PC-1
-
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
show the reaction diagram
Lactobacillus acidophilus R26
-
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
-
very slowly
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
-
PC-1
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
-
PC-1
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
-
calf, only single-stranded portion of tRNA from 3'-OH end
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
-
highly polymerized RNA: hydrolyzed at medium speed, single-stranded RNA: slowly, tRNA: not a substrate
-
-
?
RNA + H2O
RNA(n-1) + nucleoside 5'-phosphate
show the reaction diagram
Bacillus subtilis, Bacillus subtilis BG581
-
RNase J1 activity is sensitive to the phosphorylation state of the 5'-end, with severalfold greater activity observed with monophosphorylated or hydroxylated 5'-ends than with triphosphorylated 5'-ends
-
-
?
RNA + H2O
5'-GMP + 5'-AMP + ?
show the reaction diagram
-
-
-
?
thymidine 5'-monophosphate p-nitrophenylester + H2O
? + phosphate
show the reaction diagram
-
-
-
?
thymidine 5'-monophosphate p-nitrophenylester + H2O
p-nitrophenol + TMP
show the reaction diagram
-
-
-
?
thymidine 5'-triphosphate + H2O
?
show the reaction diagram
-
-
-
-
?
TpT + H2O + H2O
5'-TMP + thymidine
show the reaction diagram
-
calf
-
?
UDP-glucose + H2O
glucose-1-phosphate + 5'-UMP
show the reaction diagram
-
-
-
-
?
UDP-glucose + H2O
glucose-1-phosphate + 5'-UMP
show the reaction diagram
-
-
-
?
UDP-glucose + H2O
glucose-1-phosphate + 5'-UMP
show the reaction diagram
-
PC-1
PC-1
?
uridylyl-3',5'-adenosine + H2O
?
show the reaction diagram
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
-
-
?
UTP + H2O
UMP + diphosphate
show the reaction diagram
-
-
-
?
methyl 4-nitrophenyl phosphorothioate + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
no activity with cAMP
-
-
-
additional information
?
-
-
no activity with cAMP
-
-
-
additional information
?
-
-
no activity with dinucleotides bearing 3'-phosphate , 2': 3'-cyclic AMP and 3': 5'-cyclic AMP
-
-
-
additional information
?
-
-
no activity with dinucleotides bearing 3'-phosphate , 2': 3'-cyclic AMP and 3': 5'-cyclic AMP
-
-
-
additional information
?
-
-
no activity with 2',3'-cyclic nucleotides
-
-
-
additional information
?
-
-
no activity with dinucleotides bearing 3'-phosphate
-
-
-
additional information
?
-
-
no activity with dinucleotides bearing 3'-phosphate
-
-
-
additional information
?
-
-
enzyme does not have a strict base specificity, it does not attack oligonucleotides with a 3'-phosphate terminal
-
-
-
additional information
?
-
-
enzyme does not have a strict base specificity, it does not attack oligonucleotides with a 3'-phosphate terminal
-
-
-
additional information
?
-
-
enzyme does not have a strict base specificity, it does not attack oligonucleotides with a 3'-phosphate terminal
-
-
-
additional information
?
-
-
no activity with the cyclic trimer of deoxythymidine 5'-phosphate and adenosine 3',5'-monophosphate
-
-
-
additional information
?
-
-
no activity with cyclic nucleotides such as 2',3'-cyclic AMP, 3',5'-cyclic AMP, or 3',5'-cyclic GMP
-
-
-
additional information
?
-
-
new definition for PDE I activity which takes into account its ability to hydrolyze several types of substrates
-
-
-
additional information
?
-
-
no activity with UTP and UDP
-
-
-
additional information
?
-
-
no activity with p-nitrophenylthymidine 3'-phosphate
-
-
-
additional information
?
-
-
no activity with p-nitrophenylthymidine 3'-phosphate
-
-
-
additional information
?
-
-
no activity with p-nitrophenylthymidine 3'-phosphate
-
-
-
additional information
?
-
-
no activity with p-nitrophenylthymidine 3'-phosphate
-
-
-
additional information
?
-
-
no activity with p-nitrophenylthymidine 3'-phosphate
-
-
-
additional information
?
-
-
broad substrate specificity
-
-
-
additional information
?
-
-
broad substrate specificity
-
-
-
additional information
?
-
-
broad substrate specificity
-
-
-
additional information
?
-
-
broad substrate specificity
-
-
-
additional information
?
-
-
broad substrate specificity
-
-
-
additional information
?
-
-
overview on substrate specificity
-
?
additional information
?
-
-
study on substrate specificity and structural requirements using synthetic oligonucleotide derivatives suitable for labeling of nucleic acids
-
?
additional information
?
-
-
substrate specificity and structural requirements
-
?
additional information
?
-
-
the physiological function of PDE in plant cell is presumably the degradation of nucleic acids
-
-
-
additional information
?
-
-
phosphodiesterase activity results in the cleavage of nucleotides from nucleic acids and thus may be involved in catabolism of extracellular DNA. Essential function may be to hydrolyze polyribo- and polydeoxyribonucleotides. The enzyme may be important in cell differentiation during carcinogenesis
-
-
-
additional information
?
-
-
PC-1, PC-1 may take part in purine uptake for metabolic needs of cells
-
-
-
additional information
?
-
-
PC-1, PC-1 may take part in purine uptake for metabolic needs of cells
-
-
-
additional information
?
-
-
PC-1, plasma-membrane-associated enzyme with nucleotide pyrophosphatase/phosphodiesterase I activity is probably involved in the clearance of extracellular nucleotides such as ATP and diadenosine polyphosphates
-
-
-
additional information
?
-
-
enzyme might function as a modulating factor of platelet aggregation
-
-
-
additional information
?
-
-
enzyme may be involved in nucleotides metabolism in human plasma
-
-
-
additional information
?
-
-
the enzyme may be important in nucleotide metabolism on the cell surface
-
-
-
additional information
?
-
-
PC-1, nucleotide pyrophosphatase/alkaline phosphodiesterase I, may have a role in the regulation of N-linked glycosylation, it may regulate the availability of nucleotide sugar precusors at the site of oligosaccharide synthesis
-
-
-
additional information
?
-
-
implication of enzyme in intra- and extracellular processes, overview
-
?
additional information
?
-
-
isoform NPP1 is involved in cleavage of extracellular diadenosine polyphosphates in brain
-
-
-
additional information
?
-
-
PC-1 plays a major role in bone and cartilage metabolism by producing diphosphate
-
-
-
additional information
?
-
-
PMH hydrolyses phosphonate monoesters and phosphate diesters with similar efficiency
-
-
-
additional information
?
-
Q10Q09, Q6ZI95
NPP1 exhibits hydrolytic activity toward ADP-glucose and plastid-targeting ability
-
-
-
additional information
?
-
Q8H1D9
AtTDP has Tyr-phosphodiesterase activity for the topoisomerase-DNA complex
-
-
-
additional information
?
-
-
tyrosyl-DNA phosphodiesterase 1 catalyses the hydrolysis of phosphodiester linkages between a DNA 3' phosphate and a tyrosine residue as well as a variety of other DNA 3 substituents, the enzyme shows affinity for the substrate increased as the DNA length
-
-
-
additional information
?
-
Q10Q09, Q6ZI95
unlike isozyme NPP1, isozyme NPP3 exhibits no hydrolytic activity toward ADP-glucose and no plastid-targeting ability
-
-
-
additional information
?
-
C8CT07
product of the reaction is a 3'-phosphate and not a 3'-hydroxyl
-
-
-
additional information
?
-
-
Tdp1 activity on DNA substrate with 3'-dRP moiety in the single strand break. The 15-mer with 3'-dRP is generated by incubating 10 nM AP-DNA with EndoIII, site cleavage activity of tyrosyl-DNA phosphodiesterase 1, overview
-
-
-
additional information
?
-
-
the active site H263 is covalently bound through a phosphoamide bond to the 3' end of DNA moiety of the substrate
-
-
-
additional information
?
-
Q92484
SMPDL3A is a functional metallophosphoesterase, and despite having no detectable activity towards sphingomyelin, possesses a nucleotide phosphodiesterase activity, particularly strongly against nucleotide triphosphates
-
-
-
additional information
?
-
Q8BJ37
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
-
additional information
?
-
Q4G056
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
-
additional information
?
-
E2REL5
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
-
additional information
?
-
F1NSQ5
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
-
additional information
?
-
Q9VQM4
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
-
additional information
?
-
P38319
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues, substrates vary in size and complexity
-
-
-
additional information
?
-
Q9NUW8
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues, substrates vary in size and complexity
-
-
-
additional information
?
-
-
the enzyme catalyzes the hydrolysis of 3' phosphotyrosyl linkers and other 3'-end blocking lesions. When Top1 nicks double-stranded DNA, a covalent cleavage complex is formed that can be repaired by the enzyme, the mechanism involves the following steps: first, as Lys265 and Lys495 residues in the catalytic site coordinate the oxygen atoms of the phosphate group, His263 attacks the phosphorus atom linked to the oxygen of the Top1 catalytic residue, Tyr723, at the 3' end of DNA. Second, the TDP1-DNA covalent intermediate formed is hydrolyzed by a His493-activated water molecule, leading to the generation of a DNA product with a 3' phosphate
-
-
-
additional information
?
-
-
the enzyme cleaves the apurinic/apyrimidinic site in DNA by hydrolysis of the phosphodiester bond between the substituent and 5' adjacent phosphate. The product of enzyme cleavage in the case of the apurinic/apyrimidinic site is unstable and is hydrolyzed with the formation of 3'- and 5'-margin phosphates. The following repair demands the ordered action of polynucleotide kinase phosphorylase, with XRCC1, DNA polymerase beta, and DNA ligase, mechanism, overview
-
-
-
additional information
?
-
-
tyrosyl-DNA phosphodiesterase 1 catalyzes the hydrolysis of the phosphodiester linkage between the DNA 3'-phosphate and a tyrosine residue as well as a variety of other DNA 30 damaged termini. The enzyme can liberate the 3'-DNA phosphate termini from apurinic/apyrimidinic sites. The enzyme is more active in the cleavage of the apurinic/apyrimidinic sites inside bubble-DNA structure in comparison to ssDNA containing apurinic/apyrimidinic site, it hydrolyzes apurinic/apyrimidinic sites opposite to bulky fluorescein adduct faster than apurinic/apyrimidinic sites located in dsDNA, specificity of the apurinic/apyrimidinic site cleavage activity
-
-
-
additional information
?
-
-
tyrosyl-DNA phosphodiesterase I specifically catalyzes the hydrolysis of the phosphodiester bond between the catalytic Tyr723 of Top1 and DNA-3'-phosphate, then polynucleotide kinase phosphatase hydrolyzes the resulting 3'-phosphate end and catalyzes the phosphorylation of the 5'-hydroxyl end of the broken DNA strand. This results in a broken DNA strand with termini consisting of a 5'-phosphate and 3'-hydroxyl for DNA repair. DNA polymerase beta replaces the missing DNA segment, and finally DNA ligase III reseals the broken DNA
-
-
-
additional information
?
-
-
efficiency of apurinic/apyrimidinic site hydrolysis catalyzed by the enzyme decreases in the order: dsAP-DNA/bubble > ssAP-DNA > dsAP-DNA/Flu >> dsAP-DNA, the enzyme shows preference for 3'-substituent located on the termini of DNA compared to nicks
-
-
-
additional information
?
-
-
isozymes NPP1 and NPP3 can hydrolyze ATP, as well as inhibitor molecule 4, they also show very low activity with inhibitors 1 and 2, 1-4% compared to the activit with ATP
-
-
-
additional information
?
-
-
recombinant human enzyme processes 5'-phosphotyrosyl DNA ends when they mimic the 5'-overhangs of topoisomerase II-DNA cleavage complexes and 3'-deoxyribose phosphates generated from hydrolysis of abasic sites
-
-
-
additional information
?
-
Q92484
SMPDL3A is not an acid sphingomyelinase, but unexpectedly is active against nucleotide diphosphate and triphosphate substrates at acidic and neutral pH
-
-
-
additional information
?
-
-
substrate is 5'-[32P]-labeled single-stranded DNA oligonucleotide containing a 3'-phosphotyrosine (N14Y)
-
-
-
additional information
?
-
-
substrate is a 5'-[32P]-labeled single-stranded DNA oligonucleotide containing a 3' phosphotyrosine (N14Y)
-
-
-
additional information
?
-
Q9NUW8
the enzyme is able to act as a limited 3'-exonuclease by removing a single RNA or DNA nucleotide from the 3'-end of the DNA, but only if it bears a 3'-hydroxyl-group rather than a 3'-phosphoryl-group. The latter restriction prevents the enzyme from acting as a classic endonuclease to degrade the products of its own catalysis
-
-
-
additional information
?
-
-
the enzyme is also able to effectively cleave non-nucleotide insertions in DNA, decanediol and diethyleneglycol moieties by the same mechanism as in the case of tetrahydrofuran cleavage, it catalyzes the hydrolysis of decanediol- and bis-ethylene glycol-containing DNA even more effectively than tetrahydrofuran-containing DNA particularly in the case of decanediol-containing DNA. Repair of 5'-tetrahydrofuran and other apurinic/apyrimidinic site analogues can be processed by the long-patch base excision repair pathway, overview.The efficiency of enzyme-catalyzed hydrolysis of apurinic/apyrimidinic-site analogues correlates with the DNA helix distortion induced by the substituent
-
-
-
additional information
?
-
Mus musculus BALB/c
-
PC-1, nucleotide pyrophosphatase/alkaline phosphodiesterase I, may have a role in the regulation of N-linked glycosylation, it may regulate the availability of nucleotide sugar precusors at the site of oligosaccharide synthesis
-
-
-
additional information
?
-
Lactobacillus acidophilus R26
-
no activity with dinucleotides bearing 3'-phosphate , 2': 3'-cyclic AMP and 3': 5'-cyclic AMP, no activity with p-nitrophenylthymidine 3'-phosphate
-
-
-
additional information
?
-
Saccharomyces cerevisiae ATCC 204508
P38319
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues, substrates vary in size and complexity
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + H2O
AMP + diphosphate
show the reaction diagram
-
-
-
-
?
diadenosine polyphosphate + H2O
AMP
show the reaction diagram
-
phosphodiesterase can be considered as a catabolic enzyme
-
-
-
diadenosine polyphosphate + H2O
AMP
show the reaction diagram
-
phosphodiesterase can be considered as a catabolic enzyme
-
?
additional information
?
-
-
the physiological function of PDE in plant cell is presumably the degradation of nucleic acids
-
-
-
additional information
?
-
-
phosphodiesterase activity results in the cleavage of nucleotides from nucleic acids and thus may be involved in catabolism of extracellular DNA. Essential function may be to hydrolyze polyribo- and polydeoxyribonucleotides. The enzyme may be important in cell differentiation during carcinogenesis
-
-
-
additional information
?
-
-
PC-1, PC-1 may take part in purine uptake for metabolic needs of cells
-
-
-
additional information
?
-
-
PC-1, PC-1 may take part in purine uptake for metabolic needs of cells
-
-
-
additional information
?
-
-
PC-1, plasma-membrane-associated enzyme with nucleotide pyrophosphatase/phosphodiesterase I activity is probably involved in the clearance of extracellular nucleotides such as ATP and diadenosine polyphosphates
-
-
-
additional information
?
-
-
enzyme might function as a modulating factor of platelet aggregation
-
-
-
additional information
?
-
-
enzyme may be involved in nucleotides metabolism in human plasma
-
-
-
additional information
?
-
-
the enzyme may be important in nucleotide metabolism on the cell surface
-
-
-
additional information
?
-
-
PC-1, nucleotide pyrophosphatase/alkaline phosphodiesterase I, may have a role in the regulation of N-linked glycosylation, it may regulate the availability of nucleotide sugar precusors at the site of oligosaccharide synthesis
-
-
-
additional information
?
-
-
implication of enzyme in intra- and extracellular processes, overview
-
?
additional information
?
-
-
isoform NPP1 is involved in cleavage of extracellular diadenosine polyphosphates in brain
-
-
-
additional information
?
-
-
PC-1 plays a major role in bone and cartilage metabolism by producing diphosphate
-
-
-
additional information
?
-
Q10Q09, Q6ZI95
NPP1 exhibits hydrolytic activity toward ADP-glucose and plastid-targeting ability
-
-
-
additional information
?
-
Q8H1D9
AtTDP has Tyr-phosphodiesterase activity for the topoisomerase-DNA complex
-
-
-
additional information
?
-
-
tyrosyl-DNA phosphodiesterase 1 catalyses the hydrolysis of phosphodiester linkages between a DNA 3' phosphate and a tyrosine residue as well as a variety of other DNA 3 substituents, the enzyme shows affinity for the substrate increased as the DNA length
-
-
-
additional information
?
-
Q10Q09, Q6ZI95
unlike isozyme NPP1, isozyme NPP3 exhibits no hydrolytic activity toward ADP-glucose and no plastid-targeting ability
-
-
-
additional information
?
-
Q92484
SMPDL3A is a functional metallophosphoesterase, and despite having no detectable activity towards sphingomyelin, possesses a nucleotide phosphodiesterase activity, particularly strongly against nucleotide triphosphates
-
-
-
additional information
?
-
Q8BJ37
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
-
additional information
?
-
Q4G056
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
-
additional information
?
-
E2REL5
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
-
additional information
?
-
F1NSQ5
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
-
additional information
?
-
Q9VQM4
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
-
additional information
?
-
P38319
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues, substrates vary in size and complexity
-
-
-
additional information
?
-
Q9NUW8
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues, substrates vary in size and complexity
-
-
-
additional information
?
-
-
the enzyme catalyzes the hydrolysis of 3' phosphotyrosyl linkers and other 3'-end blocking lesions. When Top1 nicks double-stranded DNA, a covalent cleavage complex is formed that can be repaired by the enzyme, the mechanism involves the following steps: first, as Lys265 and Lys495 residues in the catalytic site coordinate the oxygen atoms of the phosphate group, His263 attacks the phosphorus atom linked to the oxygen of the Top1 catalytic residue, Tyr723, at the 3' end of DNA. Second, the TDP1-DNA covalent intermediate formed is hydrolyzed by a His493-activated water molecule, leading to the generation of a DNA product with a 3' phosphate
-
-
-
additional information
?
-
-
the enzyme cleaves the apurinic/apyrimidinic site in DNA by hydrolysis of the phosphodiester bond between the substituent and 5' adjacent phosphate. The product of enzyme cleavage in the case of the apurinic/apyrimidinic site is unstable and is hydrolyzed with the formation of 3'- and 5'-margin phosphates. The following repair demands the ordered action of polynucleotide kinase phosphorylase, with XRCC1, DNA polymerase beta, and DNA ligase, mechanism, overview
-
-
-
additional information
?
-
-
tyrosyl-DNA phosphodiesterase 1 catalyzes the hydrolysis of the phosphodiester linkage between the DNA 3'-phosphate and a tyrosine residue as well as a variety of other DNA 30 damaged termini. The enzyme can liberate the 3'-DNA phosphate termini from apurinic/apyrimidinic sites. The enzyme is more active in the cleavage of the apurinic/apyrimidinic sites inside bubble-DNA structure in comparison to ssDNA containing apurinic/apyrimidinic site, it hydrolyzes apurinic/apyrimidinic sites opposite to bulky fluorescein adduct faster than apurinic/apyrimidinic sites located in dsDNA, specificity of the apurinic/apyrimidinic site cleavage activity
-
-
-
additional information
?
-
-
tyrosyl-DNA phosphodiesterase I specifically catalyzes the hydrolysis of the phosphodiester bond between the catalytic Tyr723 of Top1 and DNA-3'-phosphate, then polynucleotide kinase phosphatase hydrolyzes the resulting 3'-phosphate end and catalyzes the phosphorylation of the 5'-hydroxyl end of the broken DNA strand. This results in a broken DNA strand with termini consisting of a 5'-phosphate and 3'-hydroxyl for DNA repair. DNA polymerase beta replaces the missing DNA segment, and finally DNA ligase III reseals the broken DNA
-
-
-
additional information
?
-
Mus musculus BALB/c
-
PC-1, nucleotide pyrophosphatase/alkaline phosphodiesterase I, may have a role in the regulation of N-linked glycosylation, it may regulate the availability of nucleotide sugar precusors at the site of oligosaccharide synthesis
-
-
-
additional information
?
-
Saccharomyces cerevisiae ATCC 204508
P38319
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues, substrates vary in size and complexity
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
(NH4)2SO4
-
slight activation
Ca2+
-
activation
Ca2+
-
slight activation
Ca2+
-
activation, 50-60 times more stimulatory than Mg2+ or Mn2+
Ca2+
-
slight activation
Ca2+
-
slight activation
Ca2+
-
slight activation
Ca2+
-
PC-1, activation
Ca2+
-
PC-1, activation
Ca2+
-
activation
Ca2+
-
activation
Ca2+
-
activation
Ca2+
-
or Mg2+, basal level required, no significant increase in activity by addition of 0.1 mM Ca2+ or Mg2+
Ca2+
-
contains 0.41 Ca2+ per protein molecule
Ca2+
-
dependent on, a calcium sensing receptor (CaSR) activation decreases cAMP and renin release and stimulates calcium calmodulin-activated phosphodiesterase
Ca2+
-
0.2 mM activity in MAA cells stimulated ca. 2fold, with calmodulin
Ca2+
-
activates
Ca2+/calmodulin
-
increased activity ca. 2.3fold
Co2+
-
slight activation
Co2+
-
no significant effect
Co2+
-
activation
Co2+
-
slight activation
Co2+
-
activation
Co2+
-
activation
Co2+
-
no activation
Cu2+
-
activation
Divalent cations
-
activation
Divalent cations
-
required for activity
Divalent cations
-
required for activity
Divalent cations
-
activation
Divalent cations
-
not required for activity
Divalent cations
-
activation
Divalent cations
-
required for activity
Divalent cations
-
required for activity
Divalent cations
-
activation
Divalent cations
-
activation; required for activity
Divalent cations
-
required for activity
Divalent cations
-
required for activity
Fe2+
-
contains 0.17 Fe2+ per protein molecule
K+
-
activation with high concentration
K+
-
slight activation
KCl
-
activation
KCl
-
slight activation
Mg2+
-
activation
Mg2+
-
slight activation
Mg2+
-
slight activation
Mg2+
-
not required for activity
Mg2+
-
slight activation
Mg2+
-
slight activation
Mg2+
-
activation
Mg2+
-
slight activation
Mg2+
-
activation
Mg2+
-
activation
Mg2+
-
slight activation
Mg2+
-
or Ca2+, basal level required, no significant increase in activity by addition of 0.1 mM Ca2+ or Mg2+
Mg2+
-
activates
MgCl2
-
activation
Mn2+
-
slight activation
Mn2+
-
activation
Mn2+
-
activation
Mn2+
-
activation
Mn2+
-
activation with low concentrations, 0.05 mM
Mn2+
P37049, P39300, P67095
activates
Mn2+
Q58346
activates, KD: 1.3 +/- 0.1 uM
Mn2+
-
Mn2+-dependent phophomonoesterase activity requires two additional amino acid residues compared with Ni2+-dependent phosphomonoester activity. Mn2+-dependent phosphodiesterase activity requires one amino acid residues less than Ni2+-dependent phosphodiesterase activity
Mn2+
-
KM value 0.022 mM
Mn2+
-
contains 0.19 Mn2+ per protein molecule, Mn2+ is the native metal ion
Na+
-
activation with high concentration
Na+
-
slight activation
NaCl
-
activation
NaCl
-
slight activation
NH4Cl
-
slight activation
Ni2+
-
slight activation
Ni2+
Q58346
activates, KD: 0.28 +/- 0.09 mM
Ni2+
-
both Ni2+-dependent phophomonoesterase activity and Ni2+-dependent phosphodiesterase activity require the same seven amino acid residues of the enzyme
Zn2+
-
activation
Zn2+
-
activation
Zn2+
-
activation
Zn2+
-
required for activity
Zn2+
-
activation; physiologically bound
Zn2+
-
activation
Zn2+
-
no activation
Zn2+
-
low concentration, 0.05 mM, 23% activation
Zn2+
-
required for activity
Zn2+
-
required, both isozymes
Zn2+
-
high affinity for Zn2+ ions, upon incubation with metal chelators, 0.76 mol Zn2+ ions are retained per mol of enzyme dimer
Zn2+
-
required for reactivation of enzyme after treatment with EDTA
Zn2+
-
enzyme carries two zinc ions per active site
Zn2+
-
contains 0.22 Zn2+ per protein molecule
Zn2+
Q92484
activates
Zn2+
-
the catalytic binding site of NPP1 contains two Zn2+ ions
Monovalent cations
-
activation with high concentrations
additional information
-
no requirement
additional information
-
hydrolysis of bis(4-nitrophenyl)phosphate requires the presence of Zn2+. Pre-5RNa processing by enzyme requires additional metal ions
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5Z)-5-(2,3,4-trihydroxybenzylidene)-1,3-thiazolidine-2,4-dithione
-
-
(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]-isoquinolin-3-yl)carbamic acid
-
-
(RP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate
-
-
(RP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate
-
-
(SP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate
-
-
(SP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate
-
-
1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
-
1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10,12-dibromo-1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10,12-dibromo-1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10,12-dibromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10,12-dibromo-1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10,12-dibromo-1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10,12-dibromo-3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10,12-dibromo-3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10-bromo-1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10-bromo-1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10-bromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10-bromo-1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10-bromo-1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10-bromo-3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
10-bromo-3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
11,13-dibromo-1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
-
11,13-dibromo-1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
11-bromo-1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
-
11-bromo-1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
2-((6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino)acetic acid
-
-
2-(3-(dimethylamino)propoxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
-
2-(3-(ethylamino)propoxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
-
2-(3-aminopropoxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
-
2-crotonyloxymethyl-(4R,5R,6R)-trihydroxy-cyclohex-2-enone
-
tumor cell line
2-mercaptoethanol
-
inactivation reversed by Zn2+
2-mercaptoethanol
-
-
2-mercaptoethanol
-
-
2-mercaptoethanol
-
-
2-mercaptoethanol
-
-
3,20-dioxopregn-4-en-21-yl 4-bromobenzenesulfonate
-
-
3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
3-(4-methoxy-phenyl)-1-(3-nitro-phenyl)-8Hpyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
3-amino-6-(3-aminopropyl)-5,6-dihydro-9-methoxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
-
-
3-amino-6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
3-cyano-6,11-dihydro-5,11-dioxo-6-[3-(dimethylaminopropyl)-5H-indeno[1,2-c]isoquinoline]
-
-
-
3-iodo-9-methoxy-6-(3-(dimethylamino)propyl)-5H-indeno-[1,2-c]isoquinoline-5,11(6H)-dione
-
-
3-isobutyl-1-methylxanthine
-
i.e. IBMX
3-methoxy-6-(3-morpholinopropyl)-2-(3-(piperidin-1-yl)-propoxy)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
-
3-methoxy-6-(3-morpholinopropyl)-2-(3-(pyrrolidin-1-yl)-propoxy)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
-
4-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoic acid
-
-
5'-deoxyribonucleotides
-
end-product inhibition
-
5'-deoxyribonucleotides
-
end-product inhibition
-
5'-deoxyribonucleotides
-
end-product inhibition
-
5'-deoxyribonucleotides
-
-
-
5'-nucleotides
-
-
5'-nucleotides
-
end-product inhibition
5'-nucleotides
-
end-product inhibition
5'-nucleotides
-
end-product inhibition
5'-nucleotides
-
end-product inhibition
5'-nucleotides
-
-
5'-nucleotides
-
-
5'-ribonucleotides
-
end-product inhibition
-
5'-ribonucleotides
-
end-product inhibition
-
5'-ribonucleotides
-
-
-
5-[3-benzyloxyphenyl]-1,3,4-oxadiazole-2(3H)-thione
-
-
5-[3-hydroxyphenyl]-1,3,4-oxadiazole-2(3H)-thione
-
-
5-[4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-oxadiazole-2(3H)-thione
-
-
5-[4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-thiadiazole-2(3H)-thione
-
-
5-[4-benzyloxyphenyl]-1,3,4-oxadiazole-2(3H)-thione
-
-
5-[4-benzyloxyphenyl]-3-octyl-1,3,4-oxadiazole-2(3H)-thione
-
-
5-[4-hydroxyphenyl]-1,3,4-oxadiazole-2(3H)-thione
-
-
5-[4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)-thione
-
-
5-[4-pyridyl]-1,3,4-oxadiazole-2(3H)-thione
-
-
5-[4-pyridyl]-1,3,4-thiadiazole-2(3H)-thione
-
-
6,6'-[propane-1,3-diylbis(iminopropane-3,1-diyl)]bis(5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione)
-
-
6-(10-aminodecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(11-aminoundecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(12-aminododecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(2-aminoethyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-(1H-imidazol-1-yl)propyl)-8-methoxy-3-nitro-5Hindeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-3-(methylamino)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-5,6-dihydro-8-methoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
-
6-(3-aminopropyl)-5,6-dihydro-9-methoxy-3-iodo-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
-
6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-7-methoxy-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-9-methoxy-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(4-aminobutyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(5-aminopentyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(6-aminohexyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(7-aminoheptyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(8-aminooctyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(9-aminononyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoic acid
-
-
8-methoxymethyl isobutylmethylxanthine
-
20 microM, 8-MM-IBMX, a selective PDE1 inhibitor, no effect on either JG cell cAMP content or renin release compared to untreated controls
8-thioadenosine 5'-triphosphate
-
-
9,11-dibromo-1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
9,11-dibromo-1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9,11-dibromo-1-(2-furyl)-3-(4-tolyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
9,11-dibromo-1-(4-chlorophenyl)-3-(4-tolyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
9,11-dibromo-1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
9,11-dibromo-1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9,11-dibromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
9,11-dibromo-1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
9,11-dibromo-1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9,11-dibromo-1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
9,11-dibromo-1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9-bromo-1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
9-bromo-1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9-bromo-1-(4-chlorophenyl)-3-(4-tolyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
9-bromo-1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
9-bromo-1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9-bromo-1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
9-bromo-1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9-bromo-1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
-
9-bromo-1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
adenosine 5'-(gamma-thio-beta,gamma-methylene)triphosphate
-
-
ADP
-
competitive
ADP
-
competitive
ADP
-
40% inhibition
ADP-ribose
-
competitive to diuridine tetraphosphate
ADPgammaS
-
-
alpha,beta-methylene-adenosine triphosphate
-
inhibition in decreasing order: alpha,beta-methyl-adenosine triphosphate, ATP, UTP, GTP, CTP
alpha,beta-methylene-ADP
-
-
AMP
-
5'-AMP and slightly 3'-AMP
AMP
-
5'-AMP, but 2'-AMP, 3'-AMP, 3': 5'cAMP and 2': 3'cAMP has no inhibiting effects; competitive; product inhibition
AMP
-
product inhibition
AMP
-
product inhibition
AMP
-
product inhibition
AMP
-
5'-AMP, competitive
AMP
-
100% inhibition
AMP
-
0.5 mM, inhibition
AMP
-
0.5 mM, 70% residual activity
AMP
-
product inhibition of NPP1
ascorbic acid
-
slight inhibition
ATP
-
competitive
ATP
-
20% inhibition
ATP
-
inhibition in decreasing order: alpha,beta-methylene-adenosine triphosphate, ATP, UTP, GTP, CTP
ATPgammaS
-
-
beta,gamma-methylene-ATP
-
-
bis(1,3,4-oxadiazol-2-methyl)-5-thione
-
-
bis(1,3,4-oxadiazol-2-propyl)-5-thione
-
-
bis(1,3,4-thiadiazole-2-methyl)-5-thione
-
-
cAMP
-
3 mM, 86% residual activity
Citric acid
-
slight inhibition
Co2+
-
-
Co2+
-
no inhibition
Co2+
-
FS-44: 5'-PDase activity of bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
CTP
-
inhibition in decreasing order: alpha,beta-methylene-adenosine triphosphate, ATP, UTP, GTP, CTP
Cu2+
-
-
Cu2+
-
purified enzyme
Cu2+
-
FS-44: 5'-PDase activity of bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
Cu2+
-
slight inhibition
CuSO4
-
-
cystine
-
slight inhibition
diadenosine polyphosphate
-
competitive
-
diethyl dicarbonate
-
-
diisopropyl fluorophosphate
-
bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
diphosphate
-
slight inhibition
dipyramidole
-
0.1 mM, inhibition, no inhibition at 0.003 mM
dithiothreitol
-
-
dithiothreitol
-
liver, spleen, thymus
dithiothreitol
-
inactivation reversed by Zn2+
dithiothreitol
-
-
dithiothreitol
-
PC-1
dofetilide
-
-
EDTA
-
-
EDTA
-
inactivation reversed by Zn2+ to 90% , by Co2+ to 40% , by Ca2+ to 25%
EDTA
-
no inhibition
EDTA
-
inactivation reversed by Mg2+, Mn2+, Ca2+, Zn2+ and slightly by Co2+
EDTA
-
PC-1, completely
EDTA
-
PC-1, nucleotide pyrophosphatase/phosphodiesterase I: glycine-enhanced inhibition, reversed by Mg2+
EDTA
-
PC-1
EDTA
-
completely, inactivation reversed by Ca2+, Co2+ and, at best, with Zn2+
EDTA
-
high concentration
EDTA
-
91% inhibition; inactivation reversed by Zn2+
EDTA
-
inactivation reversed by Zn2+
EDTA
-
complete inhibition, addition of EDTA plus Ca2+ or Mn2+ results in partial inhibition
EDTA
-
drastic reduction of activity
EGTA
-
-
ethyl 2-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]acetate
-
-
-
Fe2+
-
bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
Fe3+
-
bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase, 50% inhibition
fluoride
-
-
furamidine
-
-
-
glutathione
-
-
glutathione
-
-
glutathione
-
-
glutathione
-
-
glutathione
-
-
glycine
-
PC-1, nucleotide pyrophosphatase/phosphodiesterase I: at high concentrations, 100 mM; PC-1, nucleotide pyrophosphatase/phosphodiesterase I: glycine-enhanced inhibition by EDTA, by itself, up to 25 mM, is not inhibitory
glycine
-
liver, 0.1 M glycine, inhibition initially 20-30%, 90% inhibition obtained after 60 min preincubation
GTP
-
competitive
GTP
-
inhibition in decreasing order: alpha,beta-methylene-adenosine triphosphate, ATP, UTP, GTP, CTP
guanosine 5'-tetraphosphate
-
competitive
heparin
-
competitive
Hg2+
-
FS-44: 5'-PDase activity of bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
Hg2+
-
-
HgCl2
-
-
IBMX
-
-
IBMX
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intra peritoneal to the rats
IC86340
-
a PDE1 inhibitor, significantly reduces collagen I in human saphenous vein explants undergoing spontaneous remodeling via ex vivo culture, and acts synergistically with bicarbonate, in the absence of bicarbonate of IC86340, itself has no effect on collagen I protein. PDE1C but not PDE1A is the major isoform responsible for mediating the effects of IC86340. Lysosome inhibitors,. i.e. 2',4'-dichlorobenzamil, a nonselective CNG channel blocker, and the more specific CNG channel blocker, L-cisdiltiazem, block IC86340-mediated collagen I reduction, overview
-
indomethacin
-
-
indomethacin
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
isobutylmethylxanthine
-
100 microM, a nonselective PDE1 inhibitor, increases cAMP and renin relase by 72% and 118%, respectively
KF
-
slight inhibition
KH2PO4
-
slight inhibition
L-cysteine
-
inactivation reversed by Zn2+
L-cysteine
-
-
L-cysteine
-
-
L-cysteine
-
-
L-cysteine
-
-
methyl 2-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-2-oxoacetate
-
-
methyl 3-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoate
-
-
methyl 4-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoate
-
-
methyl 5-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoate
-
-
methyl 6-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoate
-
-
methyl-3,4-dephostatin
Q9NUW8
a dephostatin derivative, structure-activity relationship analogues of this active compound that have a chemical substitution at a single position show a dramatic decrease in inhibition activity
Mn2+
-
-
Mn2+
-
no inhibition
Mn2+
-
FS-44: 5'-PDase activity of bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
Mn2+
-
-
N-(2-[1-[2-(2-methyl-1H-imidazol-1-yl)pyrimidin-4-yl]piperidin-4-yl]ethyl)sulfuric diamide
-
-
N-(2-[1-[6-(2-methyl-1H-imidazol-1-yl)pyrimidin-4-yl]piperidin-4-yl]ethyl)sulfuric diamide
-
-
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide
-
W7, 10 microM, a calcium-calmodulin inhibitor
N-ethylmaleimide
-
tumor cell line, N-ethylmaleimide-sensitive
N-ethylmaleimide
-
lymphoblastoma; tumor cell line, N-ethylmaleimide-sensitive
N-ethylmaleimide
-
-
N-[2-(1-[6,7-dimethoxy-2-[(E)-2-(pyridin-3-yl)ethenyl]quinazolin-4-yl]piperidin-4-yl)ethyl]sulfuric diamide
-
-
N-[2-[1-(2-ethyl-6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide
-
-
N-[2-[1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide
-
enzyme binding, structure modelling, overview
N-[2-[1-(6-chloroquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide
-
-
N-[2-[1-(7-chloroquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide
-
-
N-[2-[1-(7-methoxyquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide
-
-
N-[6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide
-
-
Na3AsO4
-
slight inhibition
NAD+
-
competitive
NAD+
-
-
NAD+
-
competitive
NADH
-
-
NADP+
-
-
NADP+
-
-
NADPH
-
-
NaF
-
slight inhibition
Naphthomycin
-
tumor cell line
neomycin B
-
a aminoglycoside
Ni2+
-
-
Ni2+
-
no inhibition
NSC 88915
-
a steroid inhibitor
NSC88915
Q9NUW8
a deoxycorticosterone derivative of progesterone coupled to methyl-p-toluene-sulfonate, structure-activity relationship analogues of this active compound that have a chemical substitution at a single position show a dramatic decrease in inhibition activity
NSC88915
-
a steroid inhibitor
nucleoside 5'-triphosphate
-
-
nucleoside 5'monophosphate
-
-
nucleoside-5'-diphosphate
-
-
O-methyl O-(4-nitrophenyl) hydrogen phosphorothioate
-
-
o-phenanthroline
-
99% inhibition
p-chloromercuribenzoate
-
slight inhibition
p-Diazobenzenesulfonic acid
-
DASA: 84% inhibition
phenylalanine
-
5 mM, 87% residual activity
phenylmethylsulfonyl fluoride
-
FS-44: 5'-PDase activity of bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
phosphate
-
slight inhibition
PO43-
Q58346
competitive
Reducing agents
-
inactivation reversed by Zn2+
-
Reducing agents
-
-
-
Reducing agents
-
-
-
Reducing agents
-
-
-
RNA
-
competitive
rolipram
-
a PDE 4 inhibitor
sodium orthovanadate
-
-
suramin
-
0.25 mM, inhibition
suramin
-
0.25 mM, 87% residual activity
suramin
-
0.25 mM, about 46% inhibition
terminal 3'-monophosphoryl group of substrates
-
-
-
terminal 3'-monophosphoryl group of substrates
-
-
-
terminal 3'-monophosphoryl group of substrates
-
-
-
terminal 3'-monophosphoryl group of substrates
-
-
-
terminal 3'-monophosphoryl group of substrates
-
-
-
trequinsin
-
a PDE 3 inhibitor
tungstate
-
-
UMP
-
5'-UMP and very slightly 3'-UMP
Urea
-
slight inhibition
UTP
-
inhibition in decreasing order: alpha,beta-methylene-adenosine triphosphate, ATP, UTP, GTP, CTP
vinpocetin
-
10 mU, surpresses the increase of activity, caused by the addition of 0.2 mM Ca2+
vinpocetine
-
a PDE 1 inhibitor
vinpocetine
-
40 microM, selective PDE1 inhibitor
Zn2+
-
tumor cell line, N-ethylmaleimide-sensitive
Zn2+
-
lymphoblastoma; tumor cell line, N-ethylmaleimide-sensitive
Zn2+
-
no inhibition
Zn2+
-
FS-44: 5'-PDase activity of bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
ZnSO4
-
slight inhibition
Mn2+
-
inhibition at higher concentration, 0.1-0.5 mM
additional information
-
no inhibition by adenosine, inosine, phenylalanine and caffeine
-
additional information
-
no inhibition by anions
-
additional information
-
no inhibition by L-ascorbic acid
-
additional information
-
no inhibition by divalent cations, Mg2+ and Ca2+ , or p-chloromercuribenzoate
-
additional information
-
PC-1, no inhibition by MgCl2 and /or CaCl2
-
additional information
-
not inhibitory: 3-isobutyl-1methylxanthine, Ro 20-1724, 13-dipropyl-8-p-sulfophenylxanthine
-
additional information
-
not inhibitory: ouabain, N-ethylmaleimide, levamisole, sodium azide
-
additional information
-
not inhibitory to renal ecto-phosphodiesterase: 8-methoxymethyl-3-isobutyl-1-methylxanthine, erythro-9-(2-hydroxy-3-nonyl)adenine, milrinone, cGMP, 4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one, zaprinast, 5-nitro-2,N,N-trimethylbenzenesulfonamide
-
additional information
-
not inhibitory: levamisole, sodium azide, gadolinium chloride
-
additional information
P06802
PC-1 promoter activity induced by osteoblast differentiation is inhibited by fibroblast growth factor 2
-
additional information
-
expression of PC-1 is down-regulated during adipocyte maturation
-
additional information
-
synthesis of 1,2,9,11-tetrasubstituted 7H-thieno[2',3':4,5]pyrimido[6,1-b]-quinazolin-7-one and 1,3,10,12-tetrasubstituted 8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one inhibitors, synthesis and evaluation, overview
-
additional information
-
the enzyme is not inhibited by 5-[4-pyridyl]-1,3,4-oxadiazole-2(3H)-thione, 5-[3-benzyloxyphenyl]-1,3,4-oxadiazole-2(3H)-thione, 5-[4-benzyloxyphenyl]-3-octyl-1,3,4-oxadiazole-2(3H)-thione, 5-[4-benzyloxyphenyl]-3-benzyl-1,3,4-oxadiazole-2(3H)-thione, 5-[4-benzyloxyphenyl]-3-pentyl-1,3,4-oxadiazole-2(3H)-thione, 5-cyclohexyl-1,3,4-oxadiazole-2(3H)-thione, 5-diphenylmethyl-1,3,4-oxadiazole-2(3H)-thione, 5-[4-benzyloxyphenyl]-3-benzoyl-1,3,4-oxadiazole-2(3H)-thione, 5-[4-benzyloxyphenyl]-3-(2-hydroxyethyl)-1,3,4-oxadiazole-2(3H)-thione, 5-[1-naphthyl]-1,3,4-oxadiazole-2(3H)-thione, 5-phenyl-1,3,4-thiadiazole-2(3H)-thione, 5-[4-hydroxyphenyl]-3-benzyl-1,3,4-thiadiazole-2(3H)-thione, 5-[4-propoxyphenyl]-3-propyl-1,3,4-thiadiazole-2(3H)-thione, 5-diphenylmethyl-1,3,4-thiadiazole-2(3H)-thionr, 5-[4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)-thione, and 5-[4-benzyloxyphenyl]-3-benzyl-1,3,4-thiaadiazole-2(3H)-thione
-
additional information
-
the enzyme is not inhibited by bis(1,3,4-oxadiazol-2-methyl)-5-thione, 5-[4-pyridyl]-1,3,4-oxadiazole-2(3H)-thione, 5-[3-hydroxyphenyl]-1,3,4-oxadiazole-2(3H)-thione, 5-[4-benzyloxyphenyl]-3-octyl-1,3,4-oxadiazole-2(3H)-thione, and 5-[4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-thiadiazole-2 (3H)-thione
-
additional information
-
bicarbonate acts synergistically with inhibitor IC86340
-
additional information
-
design, synthesis, and evaluation of new indenoisoquinolines that are dual inhibitors of both tyrosyl-DNA phosphodiesterase I and topoisomerase 1, structure-activity relationships and cytotoxicity, overview. No inhibition by methyl 2-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-2-oxoacetate, methyl 3-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoate, methyl 4-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoate, methyl 5-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoate, methyl 6-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoate, 3-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]-isoquinolin-3-yl)amino]-3-oxopropanoic acid, methyl 3-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoate, methyl 4-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoate, methyl 5-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoate, 5-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoic acid, 2-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-2-oxoacetic acid, 3-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoic acid, 4-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoic acid, 5-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoic acid, 6-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoic acid, ethyl 2-[(6-Methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]acetate, 2-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]-isoquinolin-3-yl)amino]acetic acid, 2-((6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino)acetic acid, 6-(3-bromopropyl)-5,6-dihydro-8-methoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline, 6-(3-azidopropyl)-5,6-dihydro-8-methoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline, 8-methoxy-6-(3-morpholinopropyl)-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione, N-[5,11-dioxo-6-[3-(2l5-triaz-1-en-2-yn-1-yl)propyl]-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide, N-[6-(3-hydroxypropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide, N-[6-(3-aminopropyl)-11-hydroxy-5-oxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide, 6-(3-hydroxypropyl)-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione, 3-cyano-5,11-dihydro-6-[3-(1H-imidazolyl)propyl]-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinoline, 3-cyano-6,11-dihydro-5,11-dioxo-6-(3-morpholinylpropyl)-5H-indeno[1,2-c]isoquinoline, and 3-cyano-5,11-dihydro-6-[3-(dimethylamino)propyl]-5,11-dioxoindeno[1,2-c]isquinoline. Molecular modeling of the enzyme based on crystal structure PDB 1RFF
-
additional information
Q9NUW8
docking simulations suggest that enzyme inhibitors bind within the catalytic pocket to prevent docking of endogenous substrates
-
additional information
-
synthesis and evaluation of dual tyrosyl-DNA phosphodiesterase I-topoisomerase I inhibitors based on the indenoisoquinoline chemotype, structure-activity relationship studies, overview
-
additional information
-
structure-based drug design, synthesis, and biological evaluation of O-2-modified indenoisoquinolines as dual topoisomerase I-tyrosyl-DNA phosphodiesterase I inhibitors, structure-activity relationships, molecular docking studies, and molecular modeling, overview. No inhibition by 2-(allyloxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]-dioxolo[4',5':5,6]indeno [1,2-c]isoquinoline-5,12(6H)-dione, 3-methoxy-2-(3-morpholinopropoxy)-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione, 3-methoxy-2-(3-(4-methylpiperazin-1-yl)propoxy)-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]-isoquinoline-5,12(6H)-dione, methyl 2-((3-methoxy-6-(3-morpholinopropyl)-5,12-dioxo-6,12-dihydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]-isoquinolin-2-yl)oxy)acetate, and 2-((12-hydroxy-3-methoxy-6-(3-morpholinopropyl)-5-oxo-6,12-dihydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]-isoquinolin-2-yl)oxy)acetohydrazide. Antiproliferative potencies of selected O-2-modified indenoisoquinolines, overview
-
additional information
-
design and synthesis of highly potent and selective ectonucleotide pyrophosphatase/phosphodiesterase I inhibitors based on an adenosine 5-(alpha or gamma)-thio-(alpha,beta- or beta,gamma)-methylenetriphosphate scaffold, compound configurations analsis by NMR spectroscopy, overview. Analogue 4 is not a good inhibitor. The thiophosphate groups are designed to chelate the tentative Zn2+ ions. Docking od 1-3 into the NPP1 model suggests that activity correlates with the number of H-bonds with binding site residues, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3'-CMP
-
stimulate hydrolysis
Ca2+
-
maximal effect around 2 mM
dexamethasone
-
increases alkaline phosphodiesterase I in a dose- and time-dependent manner, maximal increase after treatment with 0.001 mM dexamethasone for 5 days, stimulation by dexamethasone is suppressed by cycloheximide and RU 38486
dexamethasone
-
PC-1, nucleotide pyrophosphatase/alkaline phosphodiesterase I
dithiol-stabilizing agent
-
activation
-
dithiothreitol
-
tumor cell line, N-ethylmaleimide-sensitive
fibroblast growth factor
-
-
-
Interleukin-1beta
-
-
-
Nicotinamide
-
patients with neurofibromatosis, induction of alkaline phosphodiesterase I
phorbol myristate acetate
-
-
protein kinase C activator
-
-
-
tissue necrosis factor-alpha
-
-
-
Mg2+
-
maximal effect around 2 mM
additional information
P06802
PC-1 promoter activity increases with calvarial osteoblast differentiation
-
additional information
-
insulin levels do not appear to regulate PC-1 levels in humans, PC-1 is overexpressed in patients with insulin resistance
-
additional information
-
processing by the proteasome is required for TDP1 cleavage in vivo
-
additional information
E2REL5
etoposide and doxorubicin trigger a series of events that eventually lead to an enhanced DNA-linkage of topo I, which then is acted upon by the enzyme TDP1
-
additional information
Q9VQM4
etoposide and doxorubicin trigger a series of events that eventually lead to an enhanced DNA-linkage of topo I, which then is acted upon by the enzyme TDP1
-
additional information
F1NSQ5
etoposide and doxorubicin trigger a series of events that eventually lead to an enhanced DNA-linkage of topo I, which then is acted upon by the enzyme TDP1
-
additional information
Q9NUW8
the Topo2 inhibitors etoposide, i.e. VP16, and doxorubicin, and analogues topotecan and irinotecan, trigger a series of events that eventually lead to an enhanced DNA-linkage of topo I, which then is acted upon by the enzyme TDP1, overview
-
additional information
Q8BJ37
etoposide and doxorubicin trigger a series of events that eventually lead to an enhanced DNA-linkage of topo I, which then is acted upon by the enzyme TDP1
-
additional information
Q4G056
etoposide and doxorubicin trigger a series of events that eventually lead to an enhanced DNA-linkage of topo I, which then is acted upon by the enzyme TDP1
-
additional information
P38319
the Topo2 inhibitors etoposide and doxorubicin, and analogues topotecan and irinotecan, trigger a series of events that eventually lead to an enhanced DNA-linkage of topo I, which then is acted upon by the enzyme TDP1, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
83
2-naphthyl chloromethylphosphonate
-
-
120
2-naphthyl methylphosphonate
-
-
18
2-naphthyl phenylphosphonate
-
-
0.1
3',5'-cAMP
-
-
0.26
3'-O-acetyl-p-nitrophenylthymidine 5'-phosphate
-
pH 8.0
-
4.9
4-methylumbelliferyl phenylphosphonate
-
-
8.2
4-methylumbelliferyl phenylphosphonate
-
-
0.22
4-methylumbelliferyl thymidine 5'-phosphate
-
-
2
4-methylumbelliferyl thymidine 5'-phosphate
-
-
0.96
5'-p-nitrophenyladenosine 5'-phosphate
-
FS-44: 5'-PDase activity of bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
0.2
ATP
-
-
0.8
bis(4-methylumbelliferyl) phosphate
-
-
1.2
bis(4-nitrophenyl)phosphate
-
mutant P178A, pH 7.4, 37C
1.8
bis(4-nitrophenyl)phosphate
-
mutant R252G, pH 7.4, 37C
3.5
bis(4-nitrophenyl)phosphate
-
mutant E208A, pH 7.4, 37C
6
bis(4-nitrophenyl)phosphate
-
mutant C40G, pH 7.4, 37C
6.5
bis(4-nitrophenyl)phosphate
-
mutant F51L, pH 7.4, 37C
8
bis(4-nitrophenyl)phosphate
-
mutant G62V, pH 7.4, 37C
8.5
bis(4-nitrophenyl)phosphate
-
wild-type, pH 7.4, 37C
13.2
bis(4-nitrophenyl)phosphate
-
mutant C25G, pH 7.4, 37C
22.2
bis(4-nitrophenyl)phosphate
-
mutant P64A, pH 7.4, 37C
0.25
bis(p-nitrophenyl) phosphate
-
-
0.85
bis(p-nitrophenyl) phosphate
-
-
1.6
bis(p-nitrophenyl) phosphate
-
-
2.7
bis(p-nitrophenyl) phosphate
-
-
8
bis(p-nitrophenyl) phosphate
-
milk fat globule membrane
14.4
bis(p-nitrophenyl) phosphate
-
cytoplasmic membrane of mammary gland
0.15
bis-p-nitrophenyl phosphate
Q58346
+/- 0.01, with 1 mM Ni2+
0.33
bis-p-nitrophenyl phosphate
-
pH 5.0, 60C
0.66
bis-p-nitrophenyl phosphate
Q58346
+/- 0.09, with 20 mM PO43- and 1 mM Ni2+
1.01
bis-p-nitrophenyl phosphate
Q58346
+/- 0.13, with 50 mM PO43- and 1 mM Ni2+
9.74
bis-p-nitrophenyl phosphate
-
pH 8.5, 37C
18.3
bis-p-nitrophenyl phosphate
-
pH 8.5, 37C, presence of 0.5 mM phosphate
0.001
diadenosine 5',5'''-P1,P3-triphosphate
-
Ap3A
0.0022
diadenosine 5',5'''-P1,P3-triphosphate
-
-
0.011
diadenosine 5',5'''-P1,P3-triphosphate
-
-
0.0006
diadenosine 5',5'''-P1,P4-tetraphosphate
-
Ap4A
0.002
diadenosine 5',5'''-P1,P4-tetraphosphate
-
-
0.008
diadenosine 5',5'''-P1,P4-tetraphosphate
-
-
0.012
diguanosine 5',5'''-P1,P4-tetraphosphate
-
-
0.0096
NAD+
-
-
0.03
NAD+
-
-
0.035
p-nitrophenyl 5'-thymidine monophosphate
Q58346
+/- 0.003, with 1 mM Ni2+
0.106
p-nitrophenyl 5'-thymidine monophosphate
-
pH 8.9, 37C
0.281
p-nitrophenyl 5'-thymidine monophosphate
-
pH 7.4, 37C
41
p-nitrophenyl chloromethylphosphonate
-
-
0.09
p-nitrophenyl deoxythymidine 5'-phosphate
-
-
1.7
p-nitrophenyl ethyl phosphate
-
mutant enzyme C57S, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
2.3
p-nitrophenyl ethyl phosphate
-
wild type enzyme, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
2.9
p-nitrophenyl ethyl phosphate
-
mutant enzyme C57A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
4.8
p-nitrophenyl ethyl phosphate
-
mutant enzyme T107A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
45
p-nitrophenyl ethyl phosphate
-
mutant enzyme N78A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
50
p-nitrophenyl ethyl phosphate
-
mutant enzyme Q13A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
57
p-nitrophenyl ethyl phosphate
-
mutant enzyme H218A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
70
p-nitrophenyl ethyl phosphate
-
Km above 70 mM, mutant enzyme Y105A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
73
p-nitrophenyl ethyl phosphate
-
mutant enzyme K337A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
66
p-nitrophenyl methylphosphonate
-
-
0.31
p-Nitrophenyl phenylphosphonate
-
mutant enzyme T107A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
2.8
p-Nitrophenyl phenylphosphonate
-
mutant enzyme C57A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
3
p-Nitrophenyl phenylphosphonate
-
wild type enzyme, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
3.8
p-Nitrophenyl phenylphosphonate
-
mutant enzyme C57S, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
4
p-Nitrophenyl phenylphosphonate
-
mutant enzyme N78A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
11
p-Nitrophenyl phenylphosphonate
-
-
14
p-Nitrophenyl phenylphosphonate
-
mutant enzyme K337A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
15
p-Nitrophenyl phenylphosphonate
-
-
15
p-Nitrophenyl phenylphosphonate
-
mutant enzyme H218A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
28
p-Nitrophenyl phenylphosphonate
-
mutant enzyme Y105A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
34.6
p-Nitrophenyl phenylphosphonate
-
-
43
p-Nitrophenyl phenylphosphonate
-
mutant enzyme Q13A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
152.2
p-Nitrophenyl phenylphosphonate
-
cytoplasmic membrane of mammary gland
202
p-Nitrophenyl phenylphosphonate
-
milk fat globule membrane
1.53
p-Nitrophenylphosphorylcholine
Q58346
+/- 0.1, with 20 mM Mn2+
3.33
p-Nitrophenylphosphorylcholine
Q58346
+/- 0.5, with 1 mM Ni2+
0.043
p-nitrophenylthymidine 5'-phosphate
-
-
0.046
p-nitrophenylthymidine 5'-phosphate
-
pH 9.1
0.068
p-nitrophenylthymidine 5'-phosphate
-
liver of DBA/2 mice
0.091
p-nitrophenylthymidine 5'-phosphate
-
pH 8.9, 37C
0.17
p-nitrophenylthymidine 5'-phosphate
-
pH 8.0
0.2
p-nitrophenylthymidine 5'-phosphate
-
-
0.28
p-nitrophenylthymidine 5'-phosphate
-
-
0.4
p-nitrophenylthymidine 5'-phosphate
-
-
0.41
p-nitrophenylthymidine 5'-phosphate
-
-
0.7
p-nitrophenylthymidine 5'-phosphate
-
-
1.54
p-nitrophenylthymidine 5'-phosphate
-
lymphoblastoma L5178Y
1.6
p-nitrophenylthymidine 5'-phosphate
-
milk fat globule membrane
1.7
p-nitrophenylthymidine 5'-phosphate
-
cytoplasmic membrane of mammary gland
6
p-nitrophenylthymidine 5'-phosphate
-
-
0.19
p-nitrophenyluridine 5'-phosphate
-
-
0.41
p-nitrophenyluridine 5'-phosphate
-
-
0.097
thymidine 5'-monophosphate p-nitrophenylester
-
pH 9.6, gp115, AS30D protein
0.22
thymidine 5'-monophosphate p-nitrophenylester
-
pH 9.6, gp120/gp110, liver protein
0.022
diuridine tetraphosphate
-
pH 7.4, 37C
additional information
additional information
-
kinetics of enzyme cleavage activity on different apurinic/apyrimidinic-DNA substrates., overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.8
bis(4-nitrophenyl)phosphate
-
mutant G62V, pH 7.4, 37C
1.8
bis(4-nitrophenyl)phosphate
-
mutant P178A, pH 7.4, 37C
2.3
bis(4-nitrophenyl)phosphate
-
mutant F51L, pH 7.4, 37C
3.1
bis(4-nitrophenyl)phosphate
-
mutant C40G, pH 7.4, 37C
3.9
bis(4-nitrophenyl)phosphate
-
mutant C25G, pH 7.4, 37C
4
bis(4-nitrophenyl)phosphate
-
mutant E208A, pH 7.4, 37C
4.6
bis(4-nitrophenyl)phosphate
-
mutant P64A, pH 7.4, 37C
7.4
bis(4-nitrophenyl)phosphate
-
wild-type, pH 7.4, 37C
68.5
bis(4-nitrophenyl)phosphate
-
mutant R252G, pH 7.4, 37C
19.8
bis-p-nitrophenyl phosphate
-
pH 8.5, 37C
20.3
bis-p-nitrophenyl phosphate
-
pH 8.5, 37C, presence of 0.5 mM phosphate
105.7
bis-p-nitrophenyl phosphate
Q58346
+/- 2.8, with 1 mM Ni2+
125.9
bis-p-nitrophenyl phosphate
Q58346
+/- 8.1, with 20 mM PO43- and 1 mM Ni2+
3.26
p-nitrophenyl 5'-thymidine monophosphate
Q58346
+/- 0.006, with 1mM Ni2+
0.0047
p-nitrophenyl ethyl phosphate
-
mutant enzyme C57A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
0.17
p-nitrophenyl ethyl phosphate
-
kcat below 0.17 sec-1, mutant enzyme Y105A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
0.3
p-nitrophenyl ethyl phosphate
-
mutant enzyme H218A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
0.57
p-nitrophenyl ethyl phosphate
-
mutant enzyme T107A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
1.1
p-nitrophenyl ethyl phosphate
-
mutant enzyme N78A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
1.6
p-nitrophenyl ethyl phosphate
-
mutant enzyme C57S, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
2.9
p-nitrophenyl ethyl phosphate
-
mutant enzyme K337A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
9.5
p-nitrophenyl ethyl phosphate
-
wild type enzyme, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
18
p-nitrophenyl ethyl phosphate
-
mutant enzyme Q13A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
0.0088
p-Nitrophenyl phenylphosphonate
-
mutant enzyme C57A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
1
p-Nitrophenyl phenylphosphonate
-
mutant enzyme H218A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
1.5
p-Nitrophenyl phenylphosphonate
-
mutant enzyme N78A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
2.4
p-Nitrophenyl phenylphosphonate
-
mutant enzyme T107A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
2.7
p-Nitrophenyl phenylphosphonate
-
mutant enzyme Y105A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
3.3
p-Nitrophenyl phenylphosphonate
-
mutant enzyme C57S, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
12
p-Nitrophenyl phenylphosphonate
-
mutant enzyme K337A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
16
p-Nitrophenyl phenylphosphonate
-
wild type enzyme, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
26
p-Nitrophenyl phenylphosphonate
-
mutant enzyme Q13A, at 30C, in 44 mM succinic acid, 33 mM imidazole, 33 mM diethanolamine, pH 7.5
8.6
p-Nitrophenylphosphorylcholine
Q58346
+/- 0.5, with 1 mM Ni2+
52.9
p-Nitrophenylphosphorylcholine
Q58346
+/- 1.0, with 20 mM Mn2+
130.2
bis-p-nitrophenyl phosphate
Q58346
+/- 8.6, with 50 mM PO43- and 1 mM Ni2+
0.9
additional information
-
pH 8.0, 45C, mutant H264Q, presence of Ni2+
-
1.7
additional information
-
pH 8.0, 45C, wild-type, presence of Ni2+
-
2.1
additional information
-
pH 8.0, 45C, mutant H376D, presence of Mn2+
-
2.5
additional information
-
pH 8.0, 45C, mutant D236A, presence of Ni2+
-
3 - 6
additional information
-
pH 8.0, 45C, mutant H189D, presence of Mn2+
-
3.3
additional information
-
pH 8.0, 45C, mutant H189Q, presence of Mn2+
-
3.6
additional information
-
pH 8.0, 45C, mutant R237K, presence of Ni2+
-
3.7
additional information
-
pH 8.0, 45C, mutant H189A, presence of Mn2+
-
8.8
additional information
-
pH 8.0, 45C, mutant D392E, presence of Mn2+
-
9.3
additional information
-
pH 8.0, 45C, mutant D236N, presence of Ni2+
-
12
additional information
-
pH 8.0, 45C, mutant H264N, presence of Ni2+
-
13.8
additional information
-
pH 8.0, 45C, mutant D392N, presence of Mn2+
-
18
additional information
-
pH 8.0, 45C, mutant H264A, presence of Ni2+
-
19.3
additional information
-
pH 8.0, 45C, mutant R237A, presence of Ni2+
-
23.2
additional information
-
pH 8.0, 45C, wild-type, presence of Mn2+
-
33
additional information
-
pH 8.0, 45C, mutant R237Q, presence of Ni2+
-
40.5
additional information
-
pH 8.0, 45C, mutant H376N, presence of Mn2+
-
43.5
additional information
-
pH 8.0, 45C, mutant D236A, presence of Mn2+
-
52.3
additional information
-
pH 8.0, 45C, mutant H264D, presence of Mn2+
-
65.9
additional information
-
pH 8.0, 45C, mutant D236N, presence of Mn2+
-
117.5
additional information
-
pH 8.0, 45C, mutant H189E, presence of Mn2+
-
253
additional information
-
pH 8.0, 45C, mutant H264Q, presence of Mn2+
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000685
(RP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate
-
pH 8.5, 37C, enzyme NPP1
0.0045
(RP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate
-
pH 8.5, 37C, enzyme NPP1
0.0152
(SP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate
-
pH 8.5, 37C, enzyme NPP1
0.0013
(SP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate
-
pH 8.5, 37C, enzyme NPP1
0.36
5-[3-benzyloxyphenyl]-1,3,4-oxadiazole-2(3H)-thione
-
in 20 mM Tris-HCl, pH 8.0, 0.5 M NaCl and 1 mM CaCl2, at 37C
0.36
5-[4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-oxadiazole-2(3H)-thione
-
in 20 mM Tris-HCl, pH 8.0, 0.5 M NaCl and 1 mM CaCl2, at 37C
0.85
5-[4-benzyloxyphenyl]-1,3,4-oxadiazole-2(3H)-thione
-
in 20 mM Tris-HCl, pH 8.0, 0.5 M NaCl and 1 mM CaCl2, at 37C
0.85
5-[4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)-thione
-
in 20 mM Tris-HCl, pH 8.0, 0.5 M NaCl and 1 mM CaCl2, at 37C
0.00002
adenosine 5'-(gamma-thio-beta,gamma-methylene)triphosphate
-
pH 8.5, 37C, enzyme NPP1
0.023
ADP-ribose
-
pH 7.4, 37C
0.15
bis(1,3,4-oxadiazol-2-propyl)-5-thione
-
in 20 mM Tris-HCl, pH 8.0, 0.5 M NaCl and 1 mM CaCl2, at 37C
0.0069
O-methyl O-(4-nitrophenyl) hydrogen phosphorothioate
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0006
(RP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate
-
pH 8.5, 37C, enzyme NPP1
0.0163
(RP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate
-
pH 8.5, 37C, enzyme NPP1
0.0312
(SP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate
-
pH 8.5, 37C, enzyme NPP1
0.0187
(SP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate
-
pH 8.5, 37C, enzyme NPP1
0.23
1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.3
1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.08
1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.1
1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.12
1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.07
1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.07
1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.09
1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.23
1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.06
1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.07
10,12-dibromo-1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.06
10,12-dibromo-1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.03
10,12-dibromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.05
10,12-dibromo-1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.07
10,12-dibromo-1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.08
10,12-dibromo-3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.07
10,12-dibromo-3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.1
10-bromo-1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.07
10-bromo-1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.08
10-bromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.08
10-bromo-1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.07
10-bromo-1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.1
10-bromo-3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.1
10-bromo-3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.1
11,13-dibromo-1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.13
11-bromo-1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.08
3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.0399
3-(4-methoxy-phenyl)-1-(3-nitro-phenyl)-8Hpyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
0.04
3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.494
5-[3-benzyloxyphenyl]-1,3,4-oxadiazole-2(3H)-thione
-
in 20 mM Tris-HCl, pH 8.0, 0.5 M NaCl and 1 mM CaCl2, at 37C
1
5-[3-hydroxyphenyl]-1,3,4-oxadiazole-2(3H)-thione
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.368
5-[4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-oxadiazole-2(3H)-thione
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.368
5-[4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-oxadiazole-2(3H)-thione
-
in 20 mM Tris-HCl, pH 8.0, 0.5 M NaCl and 1 mM CaCl2, at 37C
0.06647
5-[4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-thiadiazole-2(3H)-thione
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.628
5-[4-benzyloxyphenyl]-1,3,4-oxadiazole-2(3H)-thione
-
in 20 mM Tris-HCl, pH 8.0, 0.5 M NaCl and 1 mM CaCl2, at 37C
0.9
5-[4-benzyloxyphenyl]-1,3,4-oxadiazole-2(3H)-thione
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.96
5-[4-hydroxyphenyl]-1,3,4-oxadiazole-2(3H)-thione
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.39
5-[4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)-thione
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.9
5-[4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)-thione
-
in 20 mM Tris-HCl, pH 8.0, 0.5 M NaCl and 1 mM CaCl2, at 37C
0.66
5-[4-pyridyl]-1,3,4-thiadiazole-2(3H)-thione
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.998
5-[4-pyridyl]-1,3,4-thiadiazole-2(3H)-thione
-
in 20 mM Tris-HCl, pH 8.0, 0.5 M NaCl and 1 mM CaCl2, at 37C
0.00152
6,6'-[propane-1,3-diylbis(iminopropane-3,1-diyl)]bis(5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione)
-
pH 7.5, 25C, recombinant enzyme
0.014
6-(10-aminodecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
pH 7.5, 25C, recombinant enzyme
0.0128
6-(11-aminoundecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
pH 7.5, 25C, recombinant enzyme
0.0151
6-(12-aminododecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
pH 7.5, 25C, recombinant enzyme
0.0553
6-(2-aminoethyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
pH 7.5, 25C, recombinant enzyme
0.0295
6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
pH 7.5, 25C, recombinant enzyme
0.0223
6-(4-aminobutyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
pH 7.5, 25C, recombinant enzyme
0.0175
6-(5-aminopentyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
pH 7.5, 25C, recombinant enzyme
0.025
6-(6-aminohexyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
pH 7.5, 25C, recombinant enzyme
0.0288
6-(7-aminoheptyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
pH 7.5, 25C, recombinant enzyme
0.048
6-(8-aminooctyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
pH 7.5, 25C, recombinant enzyme
0.047
6-(9-aminononyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
pH 7.5, 25C, recombinant enzyme
0.1
9,11-dibromo-1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.08
9,11-dibromo-1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.337
9,11-dibromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
0.06
9,11-dibromo-1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.06
9,11-dibromo-1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.15
9-bromo-1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.09
9-bromo-1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.08
9-bromo-1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.09
9-bromo-1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
0.00039
adenosine 5'-(gamma-thio-beta,gamma-methylene)triphosphate
-
pH 8.5, 37C, enzyme NPP1
0.85
bis(1,3,4-oxadiazol-2-methyl)-5-thione
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.429
bis(1,3,4-oxadiazol-2-propyl)-5-thione
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.467
bis(1,3,4-oxadiazol-2-propyl)-5-thione
-
in 20 mM Tris-HCl, pH 8.0, 0.5 M NaCl and 1 mM CaCl2, at 37C
0.839
bis(1,3,4-thiadiazole-2-methyl)-5-thione
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.274
EDTA
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.748
L-cysteine
-
in Tris-HCl buffer 33 mM pH 8.8, at 37C
0.0004
methyl-3,4-dephostatin
Q9NUW8
pH and temperature not specified in the publication
0.00245
N-(2-[1-[2-(2-methyl-1H-imidazol-1-yl)pyrimidin-4-yl]piperidin-4-yl]ethyl)sulfuric diamide
-
-
0.0006
N-(2-[1-[6-(2-methyl-1H-imidazol-1-yl)pyrimidin-4-yl]piperidin-4-yl]ethyl)sulfuric diamide
-
-
0.000035
N-[2-(1-[6,7-dimethoxy-2-[(E)-2-(pyridin-3-yl)ethenyl]quinazolin-4-yl]piperidin-4-yl)ethyl]sulfuric diamide
-
-
0.000214
N-[2-[1-(2-ethyl-6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide
-
-
0.000036
N-[2-[1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide
-
-
0.00598
N-[2-[1-(6-chloroquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide
-
-
0.01
N-[2-[1-(7-chloroquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide
-
above
0.000187
N-[2-[1-(7-methoxyquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide
-
-
0.009
NSC88915
Q9NUW8
pH and temperature not specified in the publication
0.02
IBMX
-
60 min at 37C, 10 mM cAMP substrate, pH not specified in the publication
additional information
indomethacin
-
not tested
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0015
-
wild-type protein, in the absence of Ca2+, reflecting the basal PDE activity in the cilia, 37C, pH not specified in the publication
0.0034
-
wild-type cilial PDE, supplemented with Ca2+ and calmodulin, 2.3fold increased compared compared to the assay without Ca2+, 37C, pH not specified in the publication
0.03
-
cytoplasmic membrane of mammary gland
0.103
-
-
0.183
-
-
0.23
-
liver microsomes, substrate: p-nitrophenylthymidine 5'-phosphate
0.3
-
liver microsomes, substrate: p-nitrophenylthymidine 5'-phosphate
0.47
-
kidney microsomes, substrate: p-nitrophenylthymidine 5'-phosphate
0.48
-
substrate: NAD+
0.63
-
kidney microsomes, substrate: p-nitrophenylthymidine 5'-phosphate
1.2
-
substrate: p-nitrophenyluridine 5'-phosphate
1.88
-
substrate: ApU
2.16
-
pH 5.0, 60C
5.08
-
-
13
-
nucleotide pyrophosphatase/phosphodiesterase I
15.5 - 29
-
-
16
-
calf
47.7
-
-
125.2
-
-
253.3
-
-
411
-
PC-1, phosphodiesterase I activity, substrate: p-nitrophenylthymidine 5'-phosphate
3230
-
FS-44: 5'-PDase activity of bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
8570
-
pH 5.0, 60C
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
synthetic construct
-
kinetics
additional information
-
no basal activity is detected using the Pde1-/- knockout mutant in the standard assay and also the addition of Ca2+/calmodulin does not elicit any PDE acitivty
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5
-
immobilized enzyme
5.5
-
native enzyme
5.6
-
FS-44, 5'-PDase activity of bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
6.8
Q10Q09, Q6ZI95
assay at; assay at
7
Q92484
assay at
7.5
-
phosphomonoesterase activity, assay at
7.5
-
assay at
8 - 9
-
-
8
-
phosphodiesterase activity, assay at
8
-
assay at
8.5
-
assay at
9 - 10.5
-
-
9 - 9.1
-
-
9 - 9.1
-
-
9 - 9.1
-
nucleotide pyrophosphatase/phosphodiesterase I
9 - 9.5
-
-
9.5 - 9.6
-
-
10 - 10.5
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5
-
above, loss in activity below pH 5
5.5
-
above, the activity of phosphodiesterase increases continuously with increasing pH, from zero activity below pH 5.5
6 - 9.5
-
-
7
-
at pH 7.0 less than 10% activity of that at pH 8.5
7.5 - 10.5
-
-
7.9 - 10.5
-
-
10 - 10.2
-
narrow
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
-
assay at room temperature
30
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
Q924C3
assay at
37
-
assay at
37
Q10Q09, Q6ZI95
assay at; assay at
37
-
assay at
37
Q92484
assay at
37
-
assay at
55 - 65
-
-
60
-
FS-44, 5'-PDase activity of bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 55
-
activities at 25C: 58%, at 55C: 16%, respectively, of that at 37C
35 - 40
-
-
35 - 70
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
vulva carcinoma cells
Manually annotated by BRENDA team
-
PC-1 is either overexpressed or overactive in adipose tissue of insulin-resistant individuals both nondiabetic and diabetic
Manually annotated by BRENDA team
-
arteries from hypertensive rats, vascular PDE1A, PDE1B, PDE1C, and PDE5 isoforms
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
arteries from hypertensive rats, vascular PDE1A, PDE1B, PDE1C, and PDE5 isoforms
-
Manually annotated by BRENDA team
-
hepatocarcinoma cell line
Manually annotated by BRENDA team
Mus musculus C57/black
-
-
-
Manually annotated by BRENDA team
-
colocalization with ecto-nucleoside triphosphate diphosphohydrolase and ecto-5'-nuleotidase on platelet surface
Manually annotated by BRENDA team
-
no difference in enzyme activity between young and adult animals
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
-
highest enzyme activities in synaptic membranes from cerebellum, hypothalamus, hippocampus
Manually annotated by BRENDA team
-
high expression level
Manually annotated by BRENDA team
-
tumor-derived and normal fibroblasts, patients with neurofibromatosis
Manually annotated by BRENDA team
-
dermal fibroblasts, PC-1 is either overexpressed or overactive in fibroblasts of insulin-resistant individuals both nondiabetic and diabetic
Manually annotated by BRENDA team
-
Ltk- mouse fibroblast line
Manually annotated by BRENDA team
-
heart left ventricle, expression of isoforms NPP2 and NPP3, not NPP1. NPP3 shows the highest abundance
Manually annotated by BRENDA team
-
PLC/ PRF/5 human hepatoma
Manually annotated by BRENDA team
-
highest enzyme activities in synaptic membranes from cerebellum, hypothalamus, hippocampus
Manually annotated by BRENDA team
-
highest enzyme activities in synaptic membranes from cerebellum, hypothalamus, hippocampus
Manually annotated by BRENDA team
-
intestinal mucosa
Manually annotated by BRENDA team
-
intestinal mucosa
Manually annotated by BRENDA team
-
dithiothreitol-sensitive
Manually annotated by BRENDA team
Mus musculus C57/black
-
-
-
Manually annotated by BRENDA team
-
JG cells, isoform 1C, isolated from 8-to 10-week-old C57/BL6 mice, cells in the kidney which synthesize, store and release renin (EC 3.4.23.15)
Manually annotated by BRENDA team
-
ecto-phosphodiesterase activity is not mediated by isoform PDE1, PDE2, PDE3, PDE4, PDE5, PDE6, PDE7, PDE9, PDE10,or PDE11 activity
Manually annotated by BRENDA team
-
dithiothreitol-sensitive
Manually annotated by BRENDA team
-
human liver and liver neoplasm from human
Manually annotated by BRENDA team
-
PC-1, nucleotide pyrophosphatase/phosphodiesterase I
Manually annotated by BRENDA team
Mus musculus C57/black
-
-
-
Manually annotated by BRENDA team
-
human malignant melanoma MAA cell line
Manually annotated by BRENDA team
-
murine mouse myeloma cell line P3-X63-Ag653
Manually annotated by BRENDA team
-
mouse myeloma cell line NS-1
Manually annotated by BRENDA team
-
OSN cilia, PDE1C is detected primarily in the cilial layer, whereas PDE4A is detected in OSN cell bodies, dentrites and axons. The loss of one of the PDEs does not effect the occurrence of the other PDE. The localization of the PDE4A protein is normal in PDE1c-/- knockout mutant mice and vice versa
Manually annotated by BRENDA team
-
primary cell culture of submandibular salivary gland, co-localization of enzyme with an ecto-ATP diphosphohydrolase and an ecto-5'-nucleotidase
Manually annotated by BRENDA team
-
germinated
Manually annotated by BRENDA team
-
umbilical cord blood serum
Manually annotated by BRENDA team
-
PC-1 is either overexpressed or overactive in muscle of insulin-resistant individuals both nondiabetic and diabetic
Manually annotated by BRENDA team
-
dithiothreitol-sensitive
Manually annotated by BRENDA team
-
dithiothreitol-sensitive
Manually annotated by BRENDA team
Mus musculus BALB/c
-
MOPC 315
-
Manually annotated by BRENDA team
additional information
-
-
Manually annotated by BRENDA team
additional information
-
overview on tissue distribution
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Q10Q09, Q6ZI95
isozyme NPP1 contains a plastid-targeting signal
Manually annotated by BRENDA team
-
tumor cell line, N-ethylmaleimide-sensitive
Manually annotated by BRENDA team
-
PC-1 is a type-II membrane protein
-
Manually annotated by BRENDA team
-
N-ethylmaleimide-sensitive, lymphoblastoma L5178Y
-
Manually annotated by BRENDA team
Mus musculus BALB/c
-
PC-1, PC-1 is a type-II membrane protein
-
-
Manually annotated by BRENDA team
-
PC-1, active site of plasma-membrane-associated PC-1 appears to be located extracellularly
-
Manually annotated by BRENDA team
-
PC-1, active site of plasma-membrane-associated PC-1 appears to be located extracellularly
-
Manually annotated by BRENDA team
-
PC-1, active site of plasma-membrane-associated PC-1 appears to be located extracellularly
-
Manually annotated by BRENDA team
P70158
the enzyme is secreted
-
Manually annotated by BRENDA team
Q92484
the enzyme is secreted, secretion of SMPDL3A is increased by cholesterol, synthetic regulated by liver X receptor ligands, and cyclic AMP in primary macrophages
-
Manually annotated by BRENDA team
Mus musculus C57/black
-
the enzyme is secreted
-
-
Manually annotated by BRENDA team
-
PC-1 is a class II transmembrane glycoprotein
Manually annotated by BRENDA team
C8CT07
the enzyme harbours a nuclear localization signal at its C-terminus
Manually annotated by BRENDA team
additional information
-
-
-
Manually annotated by BRENDA team
additional information
-
overview on subcellular localization
-
Manually annotated by BRENDA team
additional information
Q10Q09, Q6ZI95
no targeting of isozyme NPP3 to plastids
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Persephonella marina (strain DSM 14350 / EX-H1)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45300
-
gel filtration
208360
53000
-
gel filtration
208393
62000
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase, gel filtration and SDS-PAGE
208374
65000
-
gel filtration
208361
67000
-
tumor cell line, N-ethylmaleimide-sensitive, gel filtration and SDS-PAGE
208356
79400
-
gel filtration
682731
80000
-
Western blot analysis of PDE 1A, 1B, and 1C to determine which phosphodiesterase isoform is involved in inhibition of renin release. In conclusion isoform 1C is expressed in isolated JG cells
710820
98000 - 115000
-
gel filtration
208366
100000
-
gel filtration and PAGE
208371
108000
-
gel filtration
208386
110000
-
gel filtration
208365
125000
-
calf, gel filtration
208372
128000
-
fetal, gel filtration
134132
140000
-
liver, gel filtration
208357
190000
-
gel filtration
208358
220000
-
PC-1, SDS-PAGE
208382
230000 - 260000
-
-
697620
230000
-
PC-1, SDS-PAGE without reduction
208376
230000
-
gel filtration
208383
240000
-
PC-1, SDS-PAGE without reduction
208377
260000
-
PC-1, SDS-PAGE without reduction
208377
430000
-
gel filtration
208373
500000
-
PC-1, gel filtration
208379
additional information
-
molecular weight higher than 100000
208392
additional information
-
-
209901
additional information
Q92484
molecular mass of secreted SMPDL3A is tissue and/or species dependent
730060
additional information
P70158
molecular mass of secreted SMPDL3A is tissue and/or species dependent
730060
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 125000, SDS-PAGE
?
-
x * 66000 + x * 45000 + x * 16000, enzyme has a complex structure, which is composed of subunits of different size, stoichiometry of the complex is still uncertain, SDS-PAGE
?
-
x * 115000, gp115, and x * 110000 + x * 120000, gp120/gp110
?
Q10Q09, Q6ZI95
x * 70000, mature isozyme NPP1, SDS-PAGE
?
Q92484
x * 52000-54000, SDS-PAGE, x * 51260, sequence calculation, x * 45000, about, deglycosylated recombinant enzyme, SDS-PAGE
?
P70158
x * 62000, about, SDS-PAGE
?
Mus musculus C57/black
-
x * 62000, about, SDS-PAGE
-
dimer
-
2 * 115000, PC-1, SDS-PAGE
dimer
-
2 * 120000, PC-1, homodimer, SDS-PAGE
dimer
-
2 * 130000, PC-1, homodimer, SDS-PAGE
dimer
-
52000 + 34000 + 16000, PDE might be a dimer with two 52000 subunits, or a heterologous trimer composed of 52000, 34000 and 16000 subunits, in the former case, one of the subunits is nicked and produced the 34000 + 16000 subunits, SDS-PAGE
dimer
-
2 * ?, identical dimer
dimer
-
NPP1, NPP2, NPP3, disulfide-linked homodimers, overview
dimer
Mus musculus BALB/c
-
2 * 115000, PC-1, SDS-PAGE
-
homodimer
-
x-ray crystallography
monomer
-
1 * 56000, SDS-PAGE
monomer
-
1 * 62000, FS-44 : bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase, SDS-PAGE
monomer
-
1 * 125000, calf, SDS-PAGE
tetramer
-
x * 118000 + x * 128000, PC-1, SDS-PAGE
tetramer
-
crystallitazion data
tetramer
-
dimer of dimers in solution, X-ray crystallography
trimer
-
52000 + 34000 + 16000, PDE might be a dimer with two 52000 subunits, or a heterologous trimer composed of 52000, 34000 and 16000 subunits, in the former case, one of the subunits is nicked and produced the 34000 + 16000 subunits, SDS-PAGE
monomer
Q58346
crystallization
additional information
synthetic construct
-
artificial molecule bearing a catalytic site and a regulatory bipyridine site
additional information
-
consists of a short N-terminal intracellular domain, a single transmembrane domain, two somatomedin-B-like domains, a catalytic domain and a C-terminal nuclease-like domain, overview
additional information
-
the enzyme is composed of two domains related by a pseudo-twofold axis of symmetry. Each domain contributes a histidine and a lysine residue to form an active site that is centrally located at the symmetry axis
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase, containing N-linked sugar chains, containing a beta-aspartyl-glycosylamine bond between innermost N-acetylglucosamine and asparagine residue
glycoprotein
-
contains approximately 21% carbohydrate
glycoprotein
-
-
glycoprotein
-
PC-1, N-linked carbohydrates comprise about 30 kDa, PC-1, type-II trans-membrane glycoprotein
glycoprotein
-
PC-1 is a class II transmembrane glycoprotein
glycoprotein
Q92484
SMPDL3A is an N-linked glycoprotein
phosphoprotein
Q9NUW8
the N-terminal region is posttranslationally modified by phosphorylation of Ser81. Enzyme phosphorylation appears to be mediated by ATM (Ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase) and is increased upon cellular treatment with camptothecin. Phosphorylation of Ser81 regulates hTdp1 targeting to sites of DNA damage and stabilizes its interaction with X-ray repair cross-complementing protein 1 (XRCC1) and/or DNA ligase III similar to how ATM-mediated phosphorylation of PNKP promotes its activity at DNA lesions
poly(ADP-ribosyl)ation
Q9NUW8
the N-terminal region is posttranslationally modified by parylation, i.e. addition of polyadenosylribose units at an undefined site. Parylation of the enzyme stimulates Tdp1 translocation to sites of DNA damage, not only increases Tdp1 protein stability but also facilitates Tdp1 interaction/complex formation with XRCC1
sumoylation
Q9NUW8
the N-terminal region is posttranslationally modified by sumoylation, i.e. addition of small ubiquitin-like protein to Lys111, the sumoylation may be involved in regulating Tdp1 recruitment to DNA lesions. The enzyme is conjugated to all three SUMO isoforms, SUMO-1, SUMO-2 and SUMO-3
glycoprotein
-
NPP2, NPP3
glycoprotein
-
PC-1, N-linked carbohydrates comprise about 20 kDa
glycoprotein
-
PC-1, containing N-linked oligosaccharides
glycoprotein
-
PC-1, N-linked carbohydrates comprise about 15 kDa
glycoprotein
-
PC-1, type-II trans-membrane glycoprotein
glycoprotein
Mus musculus BALB/c
-
PC-1, containing N-linked oligosaccharides
-
proteolytic modification
Q10Q09, Q6ZI95
clear difference between N-terminal proteolytic processing schemes to form mature enzyme proteins of isozymes NPP1 and NPP3
proteolytic modification
Q10Q09, Q6ZI95
clear difference between N-terminal proteolytic processing schemes to form mature enzyme proteins of isozymes NPP1 and NPP3. NPP1 is matured to a 70-kDa protein by two-step proteolytic processing, proprotein processing occurs post-translationally in the ER-Golgi system, overview
glycoprotein
-
both isozymes
phosphoprotein
-
gp115
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2.25 A resolution, in presence and absence of sulfate inhibitor. Protein has a beta-sandwich architecture and is a tetramer with two zinc ions per active site
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
2 - 6
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase, stable between
208374
3 - 11
-
stable between
208358
3.3 - 5.3
-
stable between
208363
5
-
immobilized enzyme very stable at
208359
5
-
inactivation below, unstable near isoelectric point of 3.85
208365
5
-
inactivation below
208368
5.1
-
stable above in cold, but rapidly and apparently irreversibly inactivated at pH 4.5
208390
5.5 - 6.5
-
stable between
208393
6 - 10
-
stable between
208368
9
-
stable at
208365
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0
-
stable
650587
40
-
below, stable for 30 min. below 40C
208393
50
-
below, enzyme is heat labile
134081
50
-
up to, metal-free enzyme is less heat stable than the native enzyme, the stability of the metal-free enzyme is restored to the level of the native enzyme by Zn2+ or Co2+
208358
50
-
15 min at 50C: activity completely lost
208393
60
-
immobilized enzyme very stable at
208359
60
-
stable below
208363
60
-
stable at, without loss of activity
208366
60
-
enzyme preincubated with Zn2+, 50% of activity remained at, in the absence of Zn2+, no activity remained at
208373
60
-
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase, stable up to
208374
66
-
stable below
208368
70
-
pH 7.3, 5 min, complete loss of activity
134081
80
-
up to
208365
80
-
0.1 M Tris-acetate buffer, pH 6.8, 5 min: only 30% loss of original activity, enzyme shows considerable heat stability
208388
additional information
-
enzyme is heat labile
134081
additional information
-
enzyme very heat labile without Zn2+
208373
additional information
-
PC-1, nucleotide pyrophosphatase/phosphodiesterase I: EDTA favors thermal inactivation, divalent cations protect from thermal inactivation
208378
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
much enzyme activity is lost upon dialysis of the preparation against destilled water
-
repeated freezing and thawing inactivate phosphodiesterase
-
stable
P37049, P39300, P67095
Zn2+ stabilizes, enzyme is very unstable in the absence of Zn2+
-
(NH4)2SO4 stabilizes
-
Mn2+ stabilizes
-
Co2+ stabilizes
-
enzyme extracted with Triton-X-100 is unstable
-
glycerol, 15%, stabilizes
-
Zn2+ stabilizes
-
dithiothreitol stabilizes
-
Mn2+ stabilizes, protects from irreversible inactivation: activity lost irreversibly when the enzyme preparation is dialyzed for 2 h against buffer that does not contain Mn2+
-
dithiothreitol stabilizes, the absence of dithiothreitol during purification results in rapid inactivation
-
Zn2+ stabilizes
-
PC-1, nucleotide pyrophosphatase/phosphodiesterase I, divalent cations protect from thermal inactivation
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acetone
-
phosphodiesterase I is destroyed during preparation of an acetone powder
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
frozen, several months without loss of activity
-
-20C, 0.01 M Tris-HCl, pH 7.6, 0.5 M KCl
-
4oC, 5% glycerol, 0.5 M NaCl, pH 7.5, no loss in activity after several months
P37049, P39300, P67095
4C, 5% glycerol, 0.5 M NaCl, pH 7.5, no loss in activity after several months
P37049, P39300, P67095
4-5C, dilute solution, loses about 5% of activity per week
-
4C, 5% glycerol, 0.5 M NaCl, pH 7.5, no loss in activity after several months
Q58346
nucleotide pyrophosphatase/phosphodiesterase I, -20C, 1 mg/ml bovine serum albumin, stable for at least 1 year
-
nucleotide pyrophosphatase/phosphodiesterase I, once thawed, 4C, 1 mg/ml bovine serum albumin, stable for at least 1 month
-
PC-1, -20C, 150 mM NaCl
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
FS-44: bifunctional enzyme: cyclic-ribonucleotide phosphomutase-5'-phosphodiesterase
-
partial, Aspergillus niger AHU 7117
-
partial, milk fat globule membrane
-
partial, mixture of 3'- and 5'-exonuclease
-
partial, patients with neurofibromatosis
-
recombinant His-tagged enzyme by nickel affinity and phosphocellulose adsorption chromatography, to homogeneity
-
recombinant His-tagged enzyme from CHO cell culture medium by nickel affinity chromatography
Q92484
recombinant His-tagged wild-type and mutant enzymes byy nickel affinity and phosphocellulose adsorption chromatography, and for the wild-type enzyme further by gel filtration and heparin affinity chromatography, to homogeneity
-
recombinant Tdp1 is purified to homogeneity
-
partial, liver
-
partial, liver; partial, lymphoblastoma L5178Y
-
PC-1, NPP/PDE, nucleotide pyrophosphatase/phosphodiesterase I
-
Strep-tactin column chromatography and Superdex 200 gel filtration
-
kidney
-
partial, kidney
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gene At5g15170 or AtTDP, DNA and amino acid sequence determination and analysis, expression of GFP-tagged AtTDP in Arabidopsis thaliana plants
Q8H1D9
gene gkt, DNA and amino acid sequence determination and analysis
-
-
P37049, P39300, P67095
recombinant expression of Homo sapiens enzyme and functional complementation of Tdp1-knock-out Gallus gallus DT40 cells
-
both Msx2 and Runx2 are recruited to a conserved core Msx2 binding site within the PC-1 gene promoter upon FGF2 stimulation, promoter analysis, overview
-
cDNA encoding PC-1; PC-1, expression in COS cells and in mouse L cells
-
expressed in Mus musculus, PC-1 overexpression impairs insulin stimulation of insulin receptor activation and downstream signalling, when PC-1 is overexpressed it inhibits insulin-induced insulin receptor beta-subunit tyrosine kinase activity.
-
expression in HEK-293 cells and HCT116 cells, quantitative real-time RT-PCR expression analysis
-
full open reading frames for PDE1C1 and PDE1C3 are cloned
-
gene SMPDL3A, quantitative real-time PCR expression analysis, recombinant His-tagged enzyme expression in CHO cells and secretion to the culture medium
Q92484
overexpression of the enzyme in HEK293 cells and CHL cells leads to increase resistance to camptothecin-induced DNA damage
Q9NUW8
recombinant expression in and functional complementation of Tdp1-knock-out Gallus gallus DT40 cells. The chicken Tdp1-/- cells complemented with human enzyme show a similar amount of TDP1 protein expression compared with human 293T cells
-
recombinant expression of His-tagged enzyme
-
recombinant expression of His-tagged wild-type and mutant enzymes
-
TDP1 overexpression in U2-OS cells
-
gene LdTdp1, DNA and amino acid sequence determination and analysis
C8CT07
cDNA encoding PC-1
-
cDNA encoding PC-1; nucleotide pyrophosphatase/alkaline phosphodiesterase I, transformed into Escherichia coli
-
cDNA encoding PC-1; PC-1, expression in COS cells and in mouse L cells
-
DNA and amino acid sequence determination and analysis; DNA and amino acid sequence determination and analysis, expression of GFP-tagged full-length isozyme NPP1 and truncated mutants in Oryza sativa cells
Q10Q09, Q6ZI95
expressed in Escherichia coli Tuner(DE3) cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
generation of single Tdp1-knock-out Gallus gallus DT40 cells and of dual Tdp1-CtIP-deficient DT40 cells
-
PDE1 mRNA expression is investigated
-
fibroblast growth factor-2, FGF2, specifically induces PC-1 expression in calvarial pre-osteoblasts, which occurs via a transcriptional mechanism involving Runx2. FGF2 promotes Msx2-stimulated PC-1 expression via Frs2/MAPK signaling, Msx2 promotes transcription of the PC-1 gene downstream of FGF2, overview. both Msx2 and Runx2 are recruited to a conserved core Msx2 binding site within the PC-1 gene promoter upon FGF2 stimulation, and that Msx2 and Runx2 function together to induce PC-1 gene expression in osteoblastic cells
-
the enzyme encoding gene is upregulated in bladder tumor versus healthy urothelium tissue. The enzyme is induced by cAMP, the up-regulation of enzyme secretion by raised cAMP levels are mediated by a PKA-independent pathway. The enzyme is strongly upregulated by cholesterol loading, increase in SMPDL3A mRNA expression due to cholesterol accumulation and by and synthetic LXR ligands
Q92484
cAMP-dependent inhibition of NPP1 expression not involving the the activator protein-1 motif present in the promoter of the rat NPP1 gene. (R,S)-Isoproterenol decreases the amount of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 protein by 75% and 81%, respectively. Contrary to downregulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 , an upregulation of glial fibrillary acidic protein, a differentiation marker for astrocytic cells is observed. Ca2+, PKA, PI 3-K/PKB/GSK-3, Epac/Rap1/PP2A and MAP kinase modules are not involved in the inhibition of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene expression
Q924C3
angiotensin II upregulates phosphodiesterase 1A expression
-
angiotensin II upregulates phosphodiesterase 1A expression
Rattus norvegicus Sprague-Dawley
-
-
cAMP-dependent inhibition of NPP1 expression not involving the the activator protein-1 motif present in the promoter of the rat NPP1 gene. (R,S)-Isoproterenol decreases the amount of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 protein by 75% and 81%, respectively. Contrary to downregulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 , an upregulation of glial fibrillary acidic protein, a differentiation marker for astrocytic cells is observed. Ca2+, PKA, PI 3-K/PKB/GSK-3, Epac/Rap1/PP2A and MAP kinase modules are not involved in the inhibition of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene expression
Rattus norvegicus Wistar
-
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C25G
-
3fold decrease in ratio kcat/KM value
C40G
-
50% decrease in ratio kcat/KM value
E208A
-
33% increase in ratio kcat/KM value
F51L
-
50% decrease in ratio kcat/KM value
P178A
-
65% increase in ratio kcat/KM value
P64A
-
75% decrease in ratio kcat/KM value
R252G
-
40fold increase in ratio kcat/KM value
H76A
-
mutant with severely reduced nuclease activity
H263A
-
the enzyme mutant retains the ability to bind an apurinic/apyrimidinic site-containing DNA, but does not reveal endonuclease activity, it fails to hydrolyze the apurinic/apyrimidinic site
H493R
-
SCAN1, the enzyme mutant retains the ability to bind an apurinic/apyrimidinic site-containing DNA, but does not reveal endonuclease activity, it fails to hydrolyze the apurinic/apyrimidinic site
K121Q
-
the mutation does not reveal evidence for association with type 2 diabetic end-stage renal disease in African-Americans
K121Q
-
the mutation is closely associated with insulin resistance, type 2 diabetes mellitus, and cardio- and nephrovascular diseases, the product of this polymorphism has a 2-3fold increased binding affinity for the insulin receptor and is more potent than the wild type PC-1 protein
C57A
-
mutant shows severely reduced activity towards p-nitrophenyl phenylphosphonate compared to the wild type enzyme
C57S
-
mutant shows reduced activity towards p-nitrophenyl phenylphosphonate compared to the wild type enzyme
H218A
-
mutant shows reduced activity towards p-nitrophenyl phenylphosphonate compared to the wild type enzyme
K337A
-
mutant shows reduced activity towards p-nitrophenyl phenylphosphonate compared to the wild type enzyme
N78A
-
mutant shows reduced activity towards p-nitrophenyl phenylphosphonate compared to the wild type enzyme
Q13A
-
mutant shows increased activity towards p-nitrophenyl phenylphosphonate compared to the wild type enzyme
T107A
-
mutant shows reduced activity towards p-nitrophenyl phenylphosphonate compared to the wild type enzyme
Y105A
-
mutant shows reduced activity towards p-nitrophenyl phenylphosphonate compared to the wild type enzyme
D236A
-
strong decrease in KM value
D236N
-
strong decrease in KM value
D392E
-
transformation of metal specificity, mutant is a Mn2+-dependent phosphodiesterase/monoesterase
D392N
-
transformation of metal and substrate specificity, mutant is a Mn2+-dependent phosphodiesterase
H189A
-
transformation of metal and substrate specificity, mutant is a Mn2+-dependent phosphodiesterase
H189D
-
transformation of metal and substrate specificity, mutant is a Mn2+-dependent phosphodiesterase. Strong stimulation of activity
H189E
-
transformation of substrate specificity, mutant is a Mn2+/Ni2+-dependent phosphodiesterase
H189Q
-
decrease in phosphodiesterase activity
H264A
-
strong stimulation of phosphodiesterase activity
H264N
-
strong stimulation of phosphodiesterase activity
H264Q
-
strong stimulation of phosphodiesterase activity
H376D
-
transformation of metal specificity, mutant is a Mn2+-dependent phosphodiesterase/monoesterase
H376N
-
transformation of metal specificity, mutant is a Mn2+-dependent phosphodiesterase/monoesterase
R237A
-
strong stimulation of phosphodiesterase activity
R237E
-
strong stimulation of phosphodiesterase activity
H182F
P38319
catalytically inactive mutant, expression of this Tdp1H182F protein does not reveal an enhanced Topo1-dependent toxicity or an increased CPT sensitivity, suggesting that sequestering of the DNA-adduct does not hinder repair by alternative pathways
H182F
Saccharomyces cerevisiae ATCC 204508
-
catalytically inactive mutant, expression of this Tdp1H182F protein does not reveal an enhanced Topo1-dependent toxicity or an increased CPT sensitivity, suggesting that sequestering of the DNA-adduct does not hinder repair by alternative pathways
-
G62V
-
80% decrease in ratio kcat/KM value
additional information
Q8H1D9
loss-of-function AtTDP mutation , genomic structure of the tdp T-DNA insertion mutant, overview. The tdp Dwarf mutant is caused by reduced cell numbers, phenotype, overview
H76A
Bacillus subtilis BG581
-
mutant with severely reduced nuclease activity
-
additional information
-
homozygous PiggyBac insertion, c03958, disrupts the 5'-UTR of gene gkt resulting in mutant flies that are defective in hydrolyzing 3'-DNA-tyrosyl residues. The phenotype iss rescued by neuronal expression of the enzyme TDP1
K121Q
-
the polymorphism in the ectonucleotide pyrophosphatase/phosphodiesterase-1 gene is associated with insulin resistance, obesity, and hepatitis C viremia and core antigen levels in chronic hepatitis C virus carriers
additional information
-
mutation of the Msx2 DNA binding site, to prevent binding of Msx2 to this site, inhibits PC-1 promoter activity in FGF2 treated MC3T3E1(C4) calvarial pre-osteoblast cells
additional information
-
knocking down TDP1 in cells expressing a dominant negative form of PARP1 and co-silencing of TDP1 and the checkpoint control gene RAD17, overview
additional information
-
overexpression and suppression of the enzyme in HCT116 cells, increased alternariol-mediated rate of DNA strand breaks in TDP1-suppressed HCT116 cells
additional information
C8CT07
construction of a series of N-terminal deletion constructs of LdTdp1 with a GFP fused at the C-terminus, expression in Leishmania donovani. This C-terminal deletion construct exhibits cytoplasmic distribution of green fluorescence
additional information
-
Pde1c-/- and Pde4a-/- knockout mutants to examine the role of the PDEs in olfactory transduction. Pde1c-/- OSNs (olfactory sensory neuron cilia) show reduced sensitivity and attenuated adaptation to repeated stimulation, suggesting that PDE1C may be involved in regulating sensitivity and adaptation
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
reactivation of enzyme after treatment with EDTA requires Zn2+
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
-
production of 5'-mononucleotides, degradation of 2',5'-dinucleotides in nuclease P1 digest of technical grade yeast RNA
biotechnology
-
study on substrate specificity and structural requirements using synthetic oligonucleotide derivatives suitable for labeling of nucleic acids
pharmacology
-
phosphodiesterase plays an important role in regulating cAMP and cGMP, und thus becomes an important site for the pharmacological intervention, i.e. Parkinson's disease, inhibition studies with thienopyrimidine fused quinazolines and pyridopyrimidine fused quinazolinones
synthesis
-
addition of autoclaved microbial cell suspensions to Catharanthus roseus cell cultures results in inhibition of growth with stimulation of enzyme production. A combination of Aleteromonas macleodii and 0.1% w/v alginate oligomers minimizes cell growth inhibition and enhances enzyme production 20times above control. Mixed alginate elecitors significantly promote phosphodiesterase production up to 120fold
analysis
-
enzyme system consisiting of phosphodiesterase and calf intestine alkaline phosphatese is used to examine the 3'-termini of strand break sites
biotechnology
-
study on substrate specificity and structural requirements using synthetic oligonucleotide derivatives suitable for labeling of nucleic acids
biotechnology
-
use of enzyme for direct detection of certain tandem DNA damage
analysis
-
useful tool in nucleic acid research, characterization of oligonucleotides and as an aid in sequence analysis
drug development
-
the enzyme is a possible target for drug design in treatment of calcium pyrophosphate dehydrate deposition disease. PC-1 interferes with insulin receptor signaling, a link between mutations in PC-1 and insulin resistance. PC-1 inhibitors may therefore also have use in treating diabetic patients
drug development
Q9NUW8
the enzyme is a a therapeutic target. It is of growing interesting in cancer treatment for its role in the repair of a variety of DNA adducts that are induced by chemotherapeutics
medicine
-
ectonucleotide pyrophospatase/phosphodiesterase and adenosine deaminase in the platelets and ectonucleotide pyrophospatase/phosphodiesterasein the serum are decreased in patients with uterine cervix neoplasia treated by conization or radiotherapy in relation to the control and non-treated group
medicine
-
single nucleotide polymorphisms of the ENPP1 gene are associated with type 2 diabetic end-stage renal disease in African-Americans
medicine
-
variants on the nucleotide pyrophosphatase/phosphodiesterase-1 gene are associated with obesity and insulin resistance, the ENPP1 rs997509T allele can predispose obese children to metabolic syndrome and mpaired glucose tolerance and this variant may drive the association between the ENPP1 121Q allele and insulin resistance
medicine
-
the enzyme is a promising and attractive target for cancer treatment
synthesis
-
immobilized enzyme: production of 5'-ribonucleotides, starting substances for the preparation of food additives and drugs
pharmacology
-
phosphodiesterase plays an important role in regulating cAMP and cGMP, und thus becomes an important site for the pharmacological intervention, i.e. Parkinson's disease, inhibition studies with theinopyrimidine fused quinazolines and pyridopyrimidine fused quinazolinones