Structural insight into repair of alkylated DNA by a new superfamily of DNA glycosylases comprising HEAT-like repeats.

ABSTRACT: 3-methyladenine DNA glycosylases initiate repair of cytotoxic and promutagenic alkylated bases in DNA. We demonstrate by comparative modelling that Bacillus cereus AlkD belongs to a new, fifth, structural superfamily of DNA glycosylases with an alpha-alpha superhelix fold comprising six HEAT-like repeats. The structure reveals a wide, positively charged groove, including a putative base recognition pocket. This groove appears to be suitable for the accommodation of double-stranded DNA with a flipped-out alkylated base. Site-specific mutagenesis within the recognition pocket identified several residues essential for enzyme activity. The results suggest that the aromatic side chain of a tryptophan residue recognizes electron-deficient alkylated bases through stacking interactions, while an i

SUBMITTER: Dalhus B 

PROVIDER: S-EPMC1874660 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature