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Literature summary for 4.2.99.18 extracted from

  • Dyakonova, E.S.; Koval, V.V.; Lomzov, A.A.; Ishchenko, A.A.; Fedorova, O.S.
    Apurinic/apyrimidinic endonuclease Apn1 from Saccharomyces cerevisiae is recruited to the nucleotide incision repair pathway Kinetic and structural features (2018), Biochimie, 152, 53-62 .
    View publication on PubMed
Search for more literature for 4.2.99.18

Protein Variants

Protein Variants Comment Organism
H83A site-directed mutagenesis, the mutation decrease the AP endonuclease activity of Apn1 owing to weak coordination of Zn2+ ions involved in enzymatic catalysis, suppressed enzymatic activity of H83A Apn1 results from the reduced number of active site Zn2+ ions. The active site of H83A Apn1 contains only two Zn2+ ions, with their positions being changed versus a trinuclear Zn2+ cluster of wild-type Apn1 Saccharomyces cerevisiae

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information stopped-flow fluorescence measurements, kinetic analysis of nucleotide incision repair (NIR) pathway compared to base excision DNA repair (BER) pathway. Rate constants of wild-type Apn1 interaction with substrate DHU(2-aPu), overview. Proposed kinetic mechanisms, containing two or three binding steps, for the interaction of wild-type Apn1 with substrate DHU(2-aPu) Saccharomyces cerevisiae

Metals/Ions

Metals/Ions Comment Organism Structure
additional information the nucleotide incision repair of the enzyme in presence of Mg2+ is unaltered, Mg2+ does not affect yeast Ape1 activity Saccharomyces cerevisiae
Zn2+ required for catalysis, molecular dynamics. The active site of H83A Apn1 contains only two Zn2+ ions, with their positions being changed versus a trinuclear Zn2+ cluster of wild-type Apn1 Saccharomyces cerevisiae

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Saccharomyces cerevisiae the nucleotide incision repair (NIR) recruiting Saccharomyces cerevisiae Apn1 proceeds via multistep rearrangements of the complex of Apn1 with a DHU-containing DNA substrate and results in the incised product of the reaction ?
-
 ?
additional information Saccharomyces cerevisiae ATCC 204508 / S288c the nucleotide incision repair (NIR) recruiting Saccharomyces cerevisiae Apn1 proceeds via multistep rearrangements of the complex of Apn1 with a DHU-containing DNA substrate and results in the incised product of the reaction ?
-
 ?

Organism

Organism UniProt Comment Textmining
Saccharomyces cerevisiae P22936
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-
Saccharomyces cerevisiae ATCC 204508 / S288c P22936
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-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information the nucleotide incision repair (NIR) recruiting Saccharomyces cerevisiae Apn1 proceeds via multistep rearrangements of the complex of Apn1 with a DHU-containing DNA substrate and results in the incised product of the reaction Saccharomyces cerevisiae ?
-
 ?
additional information substrate oligodeoxyribonucleotides (ODNs) are synthesized with a fluorescent 2-aminopurine (2-aPu) probe located either on the 5'- or 3'-side of an abasic site. Cleavage of substrates AP(2-aPu) and F(2-aPu) (F = tetrahydrofuran) in presence of Zn2+ and Mg2+ by wild-type and mutant H83A enzymes, overview. Molecular dynamics simulations elucidates the structural features of complexes of the enzyme with DHU-containing DNAs. The DNA substrate structure affects nucleotide incision repair (NIR) catalysis. Location of the 2-aPu residue near DHU decreases the efficacy of NIR activity of the WT enzyme and of H83A Apn1: nucleotide incision repair (NIR) activity of both enzymes decreases in the following descending order of substrates: DHU, DHU(2-aPu), and (2-aPu)DHU. Apn1 cannot incise the (2-aPu)DHU duplex because of the spatial structure of the (2-aPu)DHU-Apn1 complex, which is probably significantly distorted in the vicinity of the active site because two noncanonical base pairs are placed in close proximity to each other, the access of catalytically active amino acid residues and Zn2+ ions to the 5'-phosphodiester bond to be incised (located between the 2-aPu and DHU residues) might be blocked Saccharomyces cerevisiae ?
-
 ?
additional information the nucleotide incision repair (NIR) recruiting Saccharomyces cerevisiae Apn1 proceeds via multistep rearrangements of the complex of Apn1 with a DHU-containing DNA substrate and results in the incised product of the reaction Saccharomyces cerevisiae ATCC 204508 / S288c ?
-
 ?
additional information substrate oligodeoxyribonucleotides (ODNs) are synthesized with a fluorescent 2-aminopurine (2-aPu) probe located either on the 5'- or 3'-side of an abasic site. Cleavage of substrates AP(2-aPu) and F(2-aPu) (F = tetrahydrofuran) in presence of Zn2+ and Mg2+ by wild-type and mutant H83A enzymes, overview. Molecular dynamics simulations elucidates the structural features of complexes of the enzyme with DHU-containing DNAs. The DNA substrate structure affects nucleotide incision repair (NIR) catalysis. Location of the 2-aPu residue near DHU decreases the efficacy of NIR activity of the WT enzyme and of H83A Apn1: nucleotide incision repair (NIR) activity of both enzymes decreases in the following descending order of substrates: DHU, DHU(2-aPu), and (2-aPu)DHU. Apn1 cannot incise the (2-aPu)DHU duplex because of the spatial structure of the (2-aPu)DHU-Apn1 complex, which is probably significantly distorted in the vicinity of the active site because two noncanonical base pairs are placed in close proximity to each other, the access of catalytically active amino acid residues and Zn2+ ions to the 5'-phosphodiester bond to be incised (located between the 2-aPu and DHU residues) might be blocked Saccharomyces cerevisiae ATCC 204508 / S288c ?
-
 ?

Synonyms

Synonyms Comment Organism
APN1
-
 Saccharomyces cerevisiae
apurinic/apyrimidinic endonuclease
-
 Saccharomyces cerevisiae

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Saccharomyces cerevisiae

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.6
-
 assay at Saccharomyces cerevisiae

General Information

General Information Comment Organism
additional information molecular dynamics simulations elucidates the structural features of complexes of the enzyme with DHU-containing DNAs. Enzyme three-dimensional structure homology modeling using the structure of Endo IV (PDB ID 1QTW) as template Saccharomyces cerevisiae
physiological function apurinic/apyrimidinic endonuclease Apn1 of Saccharomyces cerevisiae is known as a key player of the base excision DNA repair (BER) pathway in yeast. BER is initiated by DNA glycosylases, whereas Apn1 can start DNA repair individually in the nucleotide incision repair (NIR) pathway. More delicate regulation of Apn1's NIR activity is necessary due to the more complicated kinetic mechanism, as compared to BER Saccharomyces cerevisiae