1lww

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1lww, resolution 2.1Å

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Borohydride-trapped hOgg1 Intermediate Structure Co-Crystallized with 8-bromoguanine

Contents

Overview

Most spontaneous damage to bases in DNA is corrected through the action of the base-excision DNA repair pathway. Base excision repair is initiated by DNA glycosylases, lesion-specific enzymes that intercept aberrant bases in DNA and catalyze their excision. How such proteins accomplish the feat of catalyzing no fewer than five sequential reaction steps using a single active site has been unknown. To help answer this, we report the structure of a trapped catalytic intermediate in DNA repair by human 8-oxoguanine DNA glycosylase. This structure and supporting biochemical results reveal that the enzyme sequesters the excised lesion base and exploits it as a cofactor to participate in catalysis. To our knowledge, the present example represents the first documented case of product-assisted catalysis in an enzyme-catalyzed reaction.

Disease

Known disease associated with this structure: Renal cell carcinoma, clear cell, somatic OMIM:[601982]

About this Structure

1LWW is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

Reference

Product-assisted catalysis in base-excision DNA repair., Fromme JC, Bruner SD, Yang W, Karplus M, Verdine GL, Nat Struct Biol. 2003 Mar;10(3):204-11. PMID:12592398

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