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Literature summary for 4.2.99.18 extracted from

  • Berquist, B.R.; McNeill, D.R.; Wilson, D.M.
    Characterization of abasic endonuclease activity of human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision (2008), J. Mol. Biol., 379, 17-27.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
ATP in presence of 1 mM Mg2+, Ape1 abasic endonuclease activity is stimulated (1.75- and 1.25-fold at 0.5 and 1 mM ATP concentrations). At 10 mM MgCl2, the higher concentrations of ATP has stimulatory effects on AP site incision by Ape1 Homo sapiens
DNA-dependent ATPase CSB in presence of 1 mM Mg2+, enzyme stimulates AP site incision by Ape1 in the absence of ATP on both fully paired duplex DNA (42F-42Comp) and an 11-nt bubble duplex substrate containing a centrally located abasic site (42F-42bubbleComp). When 2.5 mM ATP is included in the reactions with 1 mM MgCl2, inhibition of Ape1 incision activity is detected Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
ATP in presence of 1 mM Mg2+, Ape1 incision activity is inhibited at higher ATP concentrations (2-5 mM). Depending on the relative concentration of Mg2+, ATP can have both inhibitory and stimulatory consequences on Ape1 incision capacity Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information Steady-state kinetic analysis of Ape1 AP endonuclease activity at 10 mM Mg2+ with and without 5 mM ATP indicates a less than 2fold difference in KM-value but an 19fold enhancement in kcat in the presence of ATP, suggesting an enhancement of the catalytic reaction specifically Homo sapiens
0.0000057
-
AP-DNA-RNA 1 mM Mg2+ Homo sapiens
0.0000238
-
AP-DNA-DNA 1 mM Mg2+ Homo sapiens
0.0001792
-
34FDNA
-
Homo sapiens
0.001561
-
34FRNA
-
Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
K+ both MgCl2 and KCl strongly influence the efficiency of Ape1 as an ssDNA or dsDNA AP endonuclease Homo sapiens
Mg2+ In presence of Mg2+, ATP has complex effects on Ape1 cleavage activity. Endo- and exonuclease activity of Ape1 is found to be influenced by the MgCl2 concentration, with optimal exonuclease activity at low MgCl2 concentration (0.1-2 mM) and optimal endonuclease activity at high MgCl2 concentration (10-15 mM). Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens Ape1 has the ability to incise at AP sites in DNA conformations formed during DNA replication, transcription, and class switch recombination, and that Ape1 can endonucleolytically destroy damaged RNA ?
-
?
additional information Homo sapiens Ape1 is a multifunctional enzyme of 318 amino acids with redox-dependent regulation of transcription factors, 3' to 5' exonuclease, 3' phosphodiesterase, RNaseH and class II type AP endonuclease activities ?
-
?
additional information Homo sapiens human Ape1 is a multifunctional protein with a major role in initiating repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
-
Ape1 has only slightly more robust activity on the partial DNA-DNA duplex than on the comparable DNA/RNA duplex. Homo sapiens
additional information
-
creation of three-strand substrates provided a 2- to 2.5fold increase in the specific activity of Ape1 over the partial duplex with the abasic lesion positioned at the ssDNA-dsDNA junction (54Fendbubble18-18DNA) Homo sapiens
additional information
-
substrates with either a purine (G) or a pyrimidine (C) positioned opposite the AP site and two purines flanking the abasic site shows that Ape1 incision activity under optimal reaction conditions is two to threefold higher with the GFT-CCA, CFA-GCT, and CFT-GGA arrangements relative to GFA-CCT Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
34FDNA
-
Homo sapiens ?
-
?
34FRNA
-
Homo sapiens ?
-
?
AP-DNA-DNA synthetic DNA-DNA hybrid Homo sapiens ?
-
?
AP-DNA-RNA synthetic DNA-RNA hybrids that simulate a transcription intermediate Homo sapiens ?
-
?
additional information Ape1 has the ability to incise at AP sites in DNA conformations formed during DNA replication, transcription, and class switch recombination, and that Ape1 can endonucleolytically destroy damaged RNA Homo sapiens ?
-
?
additional information Ape1 is a multifunctional enzyme of 318 amino acids with redox-dependent regulation of transcription factors, 3' to 5' exonuclease, 3' phosphodiesterase, RNaseH and class II type AP endonuclease activities Homo sapiens ?
-
?
additional information human Ape1 is a multifunctional protein with a major role in initiating repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage Homo sapiens ?
-
?
additional information Used oligonucleotides are 54mers annealed to a complementary 18mer DNA to form the partial duplex substrates (54F-endbubble or 54F-centerbubble with 18DNA) and two 54mers annealed to create an 18-nt bubble structure (54Fendbubble or 54Fcenterbubble with 54bubble18comp). The abasic site is either centrally located (center bubble DNAs) or located at the ssDNA-dsDNA junction (end bubble DNAs). Ape1 most efficiently incised at an abasic site located centrally in the 18-nt bubble structure (54Fcenterbubble18-54bubblecomp), followed by the centrally located abasic site in the partial duplex DNA (54Fcenterbubble18-18DNA), the abasic site at an ssDNA/dsDNA junction in the bubble conformation (54Fendbubble18-54bubblecomp), and the abasic site at an ssDNA/dsDNA junction in partial duplex DNA (54Fendbubble18-18DNA) Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
APE1
-
Homo sapiens
apurinic/Apyrimidinic (AP) endonuclease 1
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
54
-
AP-DNA-RNA
-
Homo sapiens
174
-
AP-DNA-DNA
-
Homo sapiens
438
-
34FRNA
-
Homo sapiens
26500
-
34FDNA
-
Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.2
-
assay at Homo sapiens