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From Proteopedia
CRYSTAL STRUCTURE OF A COMPLEX BETWEEN THE WILD-TYPE LACTOCOCCUS LACTIS FPG (MUTM) AND AN OXIDIZED PYRIMIDINE CONTAINING DNA AT 310K
Structural highlights
FunctionFPG_LACLC 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.[1] Publication Abstract from PubMedDNA base-damage recognition in the base excision repair (BER) is a process operating on a wide variety of alkylated, oxidized and degraded bases. DNA glycosylases are the key enzymes which initiate the BER pathway by recognizing and excising the base damages guiding the damaged DNA through repair synthesis. We report here biochemical and structural evidence for the irreversible entrapment of DNA glycosylases by 5-hydroxy-5-methylhydantoin, an oxidized thymine lesion. The first crystal structure of a suicide complex between DNA glycosylase and unrepaired DNA has been solved. In this structure, the formamidopyrimidine-(Fapy) DNA glycosylase from Lactococcus lactis (LlFpg/LlMutM) is covalently bound to the hydantoin carbanucleoside-containing DNA. Coupling a structural approach by solving also the crystal structure of the non-covalent complex with site directed mutagenesis, this atypical suicide reaction mechanism was elucidated. It results from the nucleophilic attack of the catalytic N-terminal proline of LlFpg on the C5-carbon of the base moiety of the hydantoin lesion. The biological significance of this finding is discussed. 5-Hydroxy-5-methylhydantoin DNA lesion, a molecular trap for DNA glycosylases.,Le Bihan YV, Angeles Izquierdo M, Coste F, Aller P, Culard F, Gehrke TH, Essalhi K, Carell T, Castaing B Nucleic Acids Res. 2011 Aug;39(14):6277-90. Epub 2011 Apr 12. PMID:21486746[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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