Enzymes
UniProtKB help_outline | 3 proteins |
Reaction participants Show >> << Hide
- Name help_outline 2-oxoglutarate Identifier CHEBI:16810 (Beilstein: 3664503; CAS: 64-15-3) help_outline Charge -2 Formula C5H4O5 InChIKeyhelp_outline KPGXRSRHYNQIFN-UHFFFAOYSA-L SMILEShelp_outline [O-]C(=O)CCC(=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 418 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
a 1,N6-etheno-2ʼ-deoxyadenosine in double-stranded DNA
Identifier
RHEA-COMP:17903
Reactive part
help_outline
- Name help_outline 1,N6-etheno-dAMP residue Identifier CHEBI:189583 Charge -1 Formula C12H11N5O5P SMILEShelp_outline N12C=NC3=C(N=CN3[C@@H]4O[C@H](COP(*)(=O)[O-])[C@H](C4)O*)C1=NC=C2 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline O2 Identifier CHEBI:15379 (CAS: 7782-44-7) help_outline Charge 0 Formula O2 InChIKeyhelp_outline MYMOFIZGZYHOMD-UHFFFAOYSA-N SMILEShelp_outline O=O 2D coordinates Mol file for the small molecule Search links Involved in 2,648 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
a 2ʼ-deoxyadenosine in double-stranded DNA
Identifier
RHEA-COMP:17897
Reactive part
help_outline
- Name help_outline dAMP residue Identifier CHEBI:90615 Charge -1 Formula C10H11N5O5P SMILEShelp_outline NC1=NC=NC2=C1N=CN2[C@@H]3O[C@H](COP(=O)(*)[O-])[C@@H](O*)C3 2D coordinates Mol file for the small molecule Search links Involved in 8 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline CO2 Identifier CHEBI:16526 (Beilstein: 1900390; CAS: 124-38-9) help_outline Charge 0 Formula CO2 InChIKeyhelp_outline CURLTUGMZLYLDI-UHFFFAOYSA-N SMILEShelp_outline O=C=O 2D coordinates Mol file for the small molecule Search links Involved in 980 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline glyoxal Identifier CHEBI:34779 (Beilstein: 1732463; CAS: 107-22-2) help_outline Charge 0 Formula C2H2O2 InChIKeyhelp_outline LEQAOMBKQFMDFZ-UHFFFAOYSA-N SMILEShelp_outline [H]C(=O)C([H])=O 2D coordinates Mol file for the small molecule Search links Involved in 18 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline succinate Identifier CHEBI:30031 (Beilstein: 1863859; CAS: 56-14-4) help_outline Charge -2 Formula C4H4O4 InChIKeyhelp_outline KDYFGRWQOYBRFD-UHFFFAOYSA-L SMILEShelp_outline [O-]C(=O)CCC([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 325 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:70463 | RHEA:70464 | RHEA:70465 | RHEA:70466 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA.
Ringvoll J., Moen M.N., Nordstrand L.M., Meira L.B., Pang B., Bekkelund A., Dedon P.C., Bjelland S., Samson L.D., Falnes P.O., Klungland A.
Endogenous formation of the mutagenic DNA adduct 1,N(6)-ethenoadenine (epsilon A) originates from lipid peroxidation. Elevated levels of epsilon A in cancer-prone tissues suggest a role for this adduct in the development of some cancers. The base excision repair pathway has been considered the pri ... >> More
Endogenous formation of the mutagenic DNA adduct 1,N(6)-ethenoadenine (epsilon A) originates from lipid peroxidation. Elevated levels of epsilon A in cancer-prone tissues suggest a role for this adduct in the development of some cancers. The base excision repair pathway has been considered the principal repair system for epsilon A lesions until recently, when it was shown that the Escherichia coli AlkB dioxygenase could directly reverse the damage. We report here kinetic analysis of the recombinant human AlkB homologue 2 (hABH2), which is able to repair epsilon A lesions in DNA. Furthermore, cation exchange chromatography of nuclear extracts from wild-type and mABH2(-/-) mice indicates that mABH2 is the principal dioxygenase for epsilon A repair in vivo. This is further substantiated by experiments showing that hABH2, but not hABH3, is able to complement the E. coli alkB mutant with respect to its defective repair of etheno adducts. We conclude that ABH2 is active in the direct reversal of epsilon A lesions, and that ABH2, together with the alkyl-N-adenine-DNA glycosylase, which is the most effective enzyme for the repair of epsilon A, comprise the cellular defense against epsilon A lesions. << Less
Cancer Res. 68:4142-4149(2008) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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Differential repair of etheno-DNA adducts by bacterial and human AlkB proteins.
Zdzalik D., Domanska A., Prorok P., Kosicki K., van den Born E., Falnes P.O., Rizzo C.J., Guengerich F.P., Tudek B.
AlkB proteins are evolutionary conserved Fe(II)/2-oxoglutarate-dependent dioxygenases, which remove alkyl and highly promutagenic etheno(ɛ)-DNA adducts, but their substrate specificity has not been fully determined. We developed a novel assay for the repair of ɛ-adducts by AlkB enzymes using oligo ... >> More
AlkB proteins are evolutionary conserved Fe(II)/2-oxoglutarate-dependent dioxygenases, which remove alkyl and highly promutagenic etheno(ɛ)-DNA adducts, but their substrate specificity has not been fully determined. We developed a novel assay for the repair of ɛ-adducts by AlkB enzymes using oligodeoxynucleotides with a single lesion and specific DNA glycosylases and AP-endonuclease for identification of the repair products. We compared the repair of three ɛ-adducts, 1,N(6)-ethenoadenine (ɛA), 3,N(4)-ethenocytosine (ɛC) and 1,N(2)-ethenoguanine (1,N(2)-ɛG) by nine bacterial and two human AlkBs, representing four different structural groups defined on the basis of conserved amino acids in the nucleotide recognition lid, engaged in the enzyme binding to the substrate. Two bacterial AlkB proteins, MT-2B (from Mycobacterium tuberculosis) and SC-2B (Streptomyces coelicolor) did not repair these lesions in either double-stranded (ds) or single-stranded (ss) DNA. Three proteins, RE-2A (Rhizobium etli), SA-2B (Streptomyces avermitilis), and XC-2B (Xanthomonas campestris) efficiently removed all three lesions from the DNA substrates. Interestingly, XC-2B and RE-2A are the first AlkB proteins shown to be specialized for ɛ-adducts, since they do not repair methylated bases. Three other proteins, EcAlkB (Escherichia coli), SA-1A, and XC-1B removed ɛA and ɛC from ds and ssDNA but were inactive toward 1,N(2)-ɛG. SC-1A repaired only ɛA with the preference for dsDNA. The human enzyme ALKBH2 repaired all three ɛ-adducts in dsDNA, while only ɛA and ɛC in ssDNA and repair was less efficient in ssDNA. ALKBH3 repaired only ɛC in ssDNA. Altogether, we have shown for the first time that some AlkB proteins, namely ALKBH2, RE-2A, SA-2B and XC-2B can repair 1,N(2)-ɛG and that ALKBH3 removes only ɛC from ssDNA. Our results also suggest that the nucleotide recognition lid is not the sole determinant of the substrate specificity of AlkB proteins. << Less
DNA Repair 30:1-10(2015) [PubMed] [EuropePMC]
This publication is cited by 5 other entries.
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Sequence Dependent Repair of 1,<i>N</i><sup>6</sup>-Ethenoadenine by DNA Repair Enzymes ALKBH2, ALKBH3, and AlkB.
Qi R., Bian K., Chen F., Tang Q., Zhou X., Li D.
Mutation patterns of DNA adducts, such as mutational spectra and signatures, are useful tools for diagnostic and prognostic purposes. Mutational spectra of carcinogens derive from three sources: adduct formation, replication bypass, and repair. Here, we consider the repair aspect of 1,<i>N</i><sup ... >> More
Mutation patterns of DNA adducts, such as mutational spectra and signatures, are useful tools for diagnostic and prognostic purposes. Mutational spectra of carcinogens derive from three sources: adduct formation, replication bypass, and repair. Here, we consider the repair aspect of 1,<i>N</i><sup>6</sup>-ethenoadenine (εA) by the 2-oxoglutarate/Fe(II)-dependent AlkB family enzymes. Specifically, we investigated εA repair across 16 possible sequence contexts (5'/3' flanking base to εA varied as G/A/T/C). The results revealed that repair efficiency is altered according to sequence, enzyme, and strand context (ss-versus ds-DNA). The methods can be used to study other aspects of mutational spectra or other pathways of repair. << Less
Molecules 26:5285-5285(2021) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.