Structural highlights
Function[Q031W6_LACLS] Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity).[HAMAP-Rule:MF_00103][SAAS:SAAS000191_004_120556] Publication Abstract from PubMedLiving organisms protect the genome against external influences by recognizing and repairing damaged DNA. A common source of gene mutation is the oxidized guanine, which undergoes base excision repair through cleavage of the glycosidic bond between the ribose and the nucleobase of the lesion. We unravel the repair mechanism utilized by bacterial glycosylase, MutM, using quantum-chemical calculations involving more than 1000 atoms of the catalytic site. In contrast to the base-protonated pathway currently favored in the literature, we show that the initial protonation of the lesion's ribose paves the way for an almost barrier-free glycosidic cleavage. The combination of theoretical and experimental data provides further insight into the selectivity and discrimination of MutM's binding site toward various substrates. Ribose-Protonated DNA Base Excision Repair: A Combined Theoretical and Experimental Study.,Sadeghian K, Flaig D, Blank ID, Schneider S, Strasser R, Stathis D, Winnacker M, Carell T, Ochsenfeld C Angew Chem Int Ed Engl. 2014 Jul 25. doi: 10.1002/anie.201403334. PMID:25065673[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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