Information on EC 4.2.99.18 - DNA-(apurinic or apyrimidinic site) lyase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
4.2.99.18
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RECOMMENDED NAME
GeneOntology No.
DNA-(apurinic or apyrimidinic site) lyase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
beta-elimination
endonuclease activity
endonuclease reaction
exonuclease reaction
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hydrolysis
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lyase rather than hydrolase reaction
phospho-group transfer
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additional information
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APE1 possesses endonuclease, exonuclease and phosphodiesterase activity
SYSTEMATIC NAME
IUBMB Comments
DNA-(apurinic or apyrimidinic site) 5'-phosphomonoester-lyase
'Nicking' of the phosphodiester bond is due to a lyase-type reaction, not hydrolysis. This group of enzymes was previously listed as endonucleases, under EC 3.1.25.2.
CAS REGISTRY NUMBER
COMMENTARY hide
60184-90-9
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61811-29-8
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SwissProt
Manually annotated by BRENDA team
strain PS832
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
strain BW565DE3
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Manually annotated by BRENDA team
strain KSR7
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
strain D273-10B/A1
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Manually annotated by BRENDA team
identification of a new 5' exon, exon 1, in the apn1 gene. The inactivity of Schizosaccharomyces pombe Apn1 is due to a nonsense mutation in the fifth codon of this exon. Reversion of this mutation restores the AP endonuclease activity of Apn1. The apn1 nonsense mutation is only found in laboratory strains derived from L972 h- and not in unrelated isolates of Schizosaccharomyces pombe. Since all Schizosaccharomyces pombe laboratory strains originate from L972 h-, it appears that all experiments involving Schizosaccharomyces pombe have been conducted in an apn1- mutant strain with a corresponding DNA repair deficiency
SwissProt
Manually annotated by BRENDA team
strain GS-5
SwissProt
Manually annotated by BRENDA team
strain UA159 and UR100, activity is present at greater levels in cells grown at low pH than grown at pH 7
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(pT)7(p(2,3-dihydroxy-5-oxopentyl phosphate))(pT)6
?
show the reaction diagram
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?
12-mer oligodeoxyribonucleotide containing a 2'-deoxyguanosine at the natural AP site
?
show the reaction diagram
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12-mer oligodeoxyribonucleotide containing a natural AP site
?
show the reaction diagram
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the minimal kinetic model for the natural AP site incision consists of four stages corresponding to three different transient states of APE1. When the enzyme is complexed with the AP-substrate, the catalytic cycle is completed within 3 s
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?
12-mer oligodeoxyribonucleotide containing a tetrahydrofuran analogue at the natural AP site
?
show the reaction diagram
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18-mer containing P33-labeled tetrahydrofuran
?
show the reaction diagram
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?
21 bp double-stranded DNA containing an apurinic/apyrimidinic-site analogue
?
show the reaction diagram
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the affinity of EndoIV for the substrate analogue is very high and its dissociation constant is less than 0.01 microM. A C-terminal DNA-recognition loop at residues 265-269 that is only present in the long type enzymes contributes to its high affinity for apurinic/apyrimidinic sites
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?
26-bp-oligonucleotide
5'-hexachloro-fluorescein phosphoramidite-labeled 13-mer fragment + ?
show the reaction diagram
oligonucleotide containing a 5'-hexachloro-fluorescein phosphoramidite-labeled tetrahydrofuranyl residue in the middle
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?
30-mer oligonucleotide duplex DNa containing a tetrahydrofuran analogue
?
show the reaction diagram
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?
34-mer dsDNA containing an internal tetrahydrofuran
18-mer ds DNA + ?
show the reaction diagram
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?
34-mer ssDNA containing an internal tetrahydrofuran
18-mer ssDNA + ?
show the reaction diagram
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34FDNA
?
show the reaction diagram
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?
34FRNA
?
show the reaction diagram
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-
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?
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite A
?
show the reaction diagram
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?
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite G
?
show the reaction diagram
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?
35 base pair oligonucleotide containing 5,6-dihydroxy-5,6-dihydrothymine opposite A
?
show the reaction diagram
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?
35 base pair oligonucleotide containing 5,6-dihydroxy-5,6-dihydrothymine opposite G
?
show the reaction diagram
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?
37mer with AP/A
?
show the reaction diagram
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37mer with AP/C
?
show the reaction diagram
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37mer with AP/G
?
show the reaction diagram
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37mer with AP/T
?
show the reaction diagram
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37mer with dihydrouridine
?
show the reaction diagram
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43-mer oligonucleotide containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
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?
43-mer oligonucleotide containing the AP-site analog tetrahydrofuran at nt 31
?
show the reaction diagram
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?
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
?
show the reaction diagram
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?
5'-CTCTCCCTTC-8-oxo-7,8-dihydroguanine-CTCCTTTCCTCT-3'
?
show the reaction diagram
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?
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
?
show the reaction diagram
5'-Cy3-CAAGGTAGTTATCCTTG-1-Black Hole Quencher1-3'
?
show the reaction diagram
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
?
show the reaction diagram
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?
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
?
show the reaction diagram
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?
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
?
show the reaction diagram
AP DNA
fragments of DNA
show the reaction diagram
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AP sites
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?
AP-DNA
fragments of DNA
show the reaction diagram
AP-DNA-DNA
?
show the reaction diagram
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synthetic DNA-DNA hybrid
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?
AP-DNA-RNA
?
show the reaction diagram
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synthetic DNA-RNA hybrids that simulate a transcription intermediate
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?
c-myc coding region determinant mRNA
?
show the reaction diagram
c-myc RNA
?
show the reaction diagram
CAAXACCTTCATCCTTTCC
?
show the reaction diagram
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X: AP site
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?
CAXAACCTTCATCCTTTCC
?
show the reaction diagram
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X: AP site
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?
CTAGTCAXCACTGTCTGTGGATAC
?
show the reaction diagram
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X: AP site
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?
CXAAACCTTCATCCTTTCC
?
show the reaction diagram
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X: AP site
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?
DNA
fragments of DNA
show the reaction diagram
DNA containing 5-OH-C/A
?
show the reaction diagram
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DNA containing 5-OH-C/G
?
show the reaction diagram
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DNA containing an abasic site
?
show the reaction diagram
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45-mer oligomer
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?
DNA containing apurinic/apyrimidinic site
DNA fragments
show the reaction diagram
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?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
DNA containing dihydrouracil
?
show the reaction diagram
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DNA containing tamdem dihydrouracil
?
show the reaction diagram
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the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
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?
DNA containing tandem dihydrouracil
?
show the reaction diagram
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the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
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?
DNA with 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine/C
?
show the reaction diagram
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DNA with 2-deoxyribonolactone
?
show the reaction diagram
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DNA with 5,6-dihydrothymidine/A
?
show the reaction diagram
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DNA with 5,6-dihydrothymine
?
show the reaction diagram
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DNA with 5,6-dihydrouracil
?
show the reaction diagram
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DNA with 5-hydroxy-2'-deoxyuridine/G
?
show the reaction diagram
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DNA with 5-hydroxy-5-methylhydantoin
?
show the reaction diagram
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DNA with 5-hydroxy-6-hydrothymine
?
show the reaction diagram
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DNA with 5-hydroxy-6-hydrouracil
?
show the reaction diagram
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DNA with alloxan
?
show the reaction diagram
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DNA with an abasic site
?
show the reaction diagram
DNA with an abasic site
DNA with 5'-phosphate terminus + DNA with 3'-alpha,beta-unsaturated aldehyde
show the reaction diagram
DNA with dihydrouridine/G
?
show the reaction diagram
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DNA with tetrahydrofuranyl/G
?
show the reaction diagram
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DNA with thymine glycol
?
show the reaction diagram
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DNA with uracil glycol
?
show the reaction diagram
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double-stranded DNA with abasic sites
?
show the reaction diagram
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?
duplex oligonucleotide containing a 5,6-dihydro-2'-deoxyuridine*G pair
?
show the reaction diagram
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nucleotide incison repair activity
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?
duplex oligonucleotide containing a alpha-2'-deoxyadenosine*T pair
?
show the reaction diagram
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nucleotide incison repair activity
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?
duplex oligonucleotide containing a tetrahydrofuran*G pair
?
show the reaction diagram
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nucleotide incison repair activity
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?
GTACGTAXCCACAGACAGTGATGA
?
show the reaction diagram
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X: AP site
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?
linear 31-mer duplex oligonucleotide (3'-32P-labeled top strand contains an abasic site at position 17)
3'-32P-labeled 14-mer oligonucleotide
show the reaction diagram
-
cleavage 3' to the apurinic/apyrimidinic site
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?
oligodeoxynucleotide with abasic site 2,3-dihydroxy-5-oxopentyl phosphate
?
show the reaction diagram
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?
oligomer with G/U pair
?
show the reaction diagram
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Red substrate 2
?
show the reaction diagram
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?
single-stranded DNA with abasic sites
?
show the reaction diagram
-
catalytic efficiency is 20fold less than the activity against double-stranded DNA with abasic sites
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?
THF-containing oligonucleotide
?
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
AP DNA
fragments of DNA
show the reaction diagram
-
AP sites
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-
?
AP-DNA
fragments of DNA
show the reaction diagram
DNA
fragments of DNA
show the reaction diagram
DNA containing apurinic/apyrimidinic site
DNA fragments
show the reaction diagram
-
-
-
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?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
DNA containing tamdem dihydrouracil
?
show the reaction diagram
-
the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
-
-
?
DNA containing tandem dihydrouracil
?
show the reaction diagram
-
the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
-
-
?
DNA with an abasic site
?
show the reaction diagram
DNA with an abasic site
DNA with 5'-phosphate terminus + DNA with 3'-alpha,beta-unsaturated aldehyde
show the reaction diagram
O29876
the enzyme excises an oxidatively-damaged form of guanine. Bifunctional enzyme with both DNA glycosylase and apurinic/apyrimidinic lyase activities
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?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe
-
pro-inflammatory activity of iron in the lung injury, at least in part, because of its induction of APE/Ref-1
MgCl2
-
tetrahydrofuran*G incision is efficiently catalyzed at 0.001 mM Mg2+, 5 mM MgCl2 are required for optimal AP endonuclease activity
Na+
-
65 mM included in assay medium
Sm2+
-
the divalent metal ion soaked with the protein crystals is found specifically to associate with the glutamate residue
additional information