3bu0
crystal structure of human ABH2 cross-linked to dsDNA with cofactors
OverviewOverview
Escherichia coli AlkB and its human homologues ABH2 and ABH3 repair DNA/RNA base lesions by using a direct oxidative dealkylation mechanism. ABH2 has the primary role of guarding mammalian genomes against 1-meA damage by repairing this lesion in double-stranded DNA (dsDNA), whereas AlkB and ABH3 preferentially repair single-stranded DNA (ssDNA) lesions and can repair damaged bases in RNA. Here we show the first crystal structures of AlkB-dsDNA and ABH2-dsDNA complexes, stabilized by a chemical cross-linking strategy. This study reveals that AlkB uses an unprecedented base-flipping mechanism to access the damaged base: it squeezes together the two bases flanking the flipped-out one to maintain the base stack, explaining the preference of AlkB for repairing ssDNA lesions over dsDNA ones. In addition, the first crystal structure of ABH2, presented here, provides a structural basis for designing inhibitors of this human DNA repair protein.
About this StructureAbout this Structure
3BU0 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA., Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, He C, Nature. 2008 Apr 24;452(7190):961-5. PMID:18432238 Page seeded by OCA on Wed Jun 11 10:57:31 2008