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Literature summary for 4.2.99.18 extracted from

  • Kuznetsov, N.A.; Kupryushkin, M.S.; Abramova, T.V.; Kuznetsova, A.A.; Miroshnikova, A.D.; Stetsenko, D.A.; Pyshnyi, D.V.; Fedorova, O.S.
    New oligonucleotide derivatives as unreactive substrate analogues and potential inhibitors of human apurinic/apyrimidinic endonuclease APE1 (2016), Mol. Biosyst., 12, 67-75 .
    View publication on PubMed
Search for more literature for 4.2.99.18

Inhibitors

Inhibitors Comment Organism Structure
DNA duplex F30N/GO
-
 Homo sapiens
DNA duplex FBB/GB
-
 Homo sapiens
DNA duplex FN/GO
-
 Homo sapiens
DNA duplex FNB/GB
-
 Homo sapiens
DNA duplex FS/GO
-
 Homo sapiens
F30N oligonucleotide
-
 Homo sapiens
FBB oligonucleotide
-
 Homo sapiens
FN oligonucleotide
-
 Homo sapiens
FNB oligonucleotide
-
 Homo sapiens
FS oligonucleotide
-
 Homo sapiens
FSS oligonucleotide
-
 Homo sapiens
GB oligonucleotide
-
 Homo sapiens
GS oligonucleotide
-
 Homo sapiens
additional information preparation of modified oligonucleotide derivatives as unreactive substrate analogues of human apurinic/apyrimidinic endonuclease APE1 for rational design of enzyme inhibitors or as potential APE1 inhibitors themselves. The 3'-terminal internucleotide phosphate group is chemically modified by the replacement of its oxygen atom by either a sulphur or a Tmg group to make the phosphate resistant to the exonuclease activity of the enzyme. Instead of the natural AP-site, the oligonucleotides incorporate its chemically stable analogue (2R,3S)-2-(hydroxymethyl)-3-hydroxytetrahydrofuran (F-site). It is known that such a substitution scarcely affects the activity of APE1. Structure of the F-site and chemical modifications of the phosphate group on its 5'-side that are resistant to APE1 hydrolysis, overview. The endonuclease activity of APE1 is considerably retarded for DNA duplexes containing phosphate modifications on the 5'-side of the F-site. But analysis of the products of chain scission of those duplexes reveals that some 3'-5'-exonuclease reaction, that removes the 3'-terminal nucleotide, also occurs. To suppress the removal of the 3'-terminal nucleotide from the model oligonucleotides, their 3'-terminal internucleotide phosphate group is modified. The tetramethyl phosphoryl guanidine group (Tmg) is employed as a nuclease-resistant phosphate group isostere. It is observed that such a modification blocks 3'-5'-exonuclease activity of APE1 for more than 12 h Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information rate constants of DNA substrate cleavage by APE1 and dissociation constants of APE1/DNA substrate complexes. Analysis of efficacy of APE1 binding to modified DNA duplexes and kinetics of enzyme-substrate complex formation by stopped flow measurements, kinetics, overview Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P27695
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information APE1 the base excision DNA repair system catalyzes the hydrolysis of the phosphodiester bond on the 5'-side of an apurinic/apyrimidinic site (AP-site) to give the 5'-phosphate and 3'-hydroxyl group. APE1 exhibits also 3'-5'-exonuclease activity albeit less pronounced compared to its endonuclease activity Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
APE1
-
 Homo sapiens
apurinic/apyrimidinic endonuclease
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Homo sapiens

General Information

General Information Comment Organism
physiological function human apurinic/apyrimidinic endonuclease APE1 is one of the key enzymes of the base excision DNA repair system. The main biological function of APE1 is the hydrolysis of the phosphodiester bond on the 5'-side of an apurinic/apyrimidinic site (AP-site) to give the 5'-phosphate and 3'-hydroxyl group. The level of enzymatic activity of human AP-endonuclease APE1 has a considerable influence on the process of the removal of DNA lesions. APE1 is an extremely active enzyme which is able to process many synthetic analogues of the AP-site such as tetrahydrofuran (F-site) or alpha,omega-alkane diols Homo sapiens