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2jhj

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Image:2jhj.gif

2jhj, resolution 1.90Å

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3-METHYLADENINE DNA-GLYCOSYLASE FROM ARCHAEOGLOBUS FULGIDUS

Overview

N(1)-methyladenine (m(1)A) and N(3)-methylcytosine (m(3)C) are major toxic and mutagenic lesions induced by alkylation in single-stranded DNA. In bacteria and mammals, m(1)A and m(3)C were recently shown to be repaired by AlkB-mediated oxidative demethylation, a direct DNA damage reversal mechanism. No AlkB gene homologues have been identified in Archaea. We report that m(1)A and m(3)C are repaired by the AfAlkA base excision repair glycosylase of Archaeoglobus fulgidus, suggesting a different repair mechanism for these lesions in the third domain of life. In addition, AfAlkA was found to effect a robust excision of 1,N(6)-ethenoadenine. We present a high-resolution crystal structure of AfAlkA, which, together with the characterization of several site-directed mutants, forms a molecular rationalization for the newly discovered base excision activity.

About this Structure

2JHJ is a Single protein structure of sequence from Archaeoglobus fulgidus with and as ligands. Active as DNA-3-methyladenine glycosylase II, with EC number 3.2.2.21 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structural basis for enzymatic excision of N1-methyladenine and N3-methylcytosine from DNA., Leiros I, Nabong MP, Grosvik K, Ringvoll J, Haugland GT, Uldal L, Reite K, Olsbu IK, Knaevelsrud I, Moe E, Andersen OA, Birkeland NK, Ruoff P, Klungland A, Bjelland S, EMBO J. 2007 Apr 18;26(8):2206-17. Epub 2007 Mar 29. PMID:17396151

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