3BKZ

X-ray structure of E coli AlkB crosslinked to dsDNA in the active site

Summary for 3BKZ

• Entry DOI: 10.2210/pdb3bkz/pdb
• Related: 2FD8 2QXQ
• Descriptor: Alpha-ketoglutarate-dependent dioxygenase alkB, DNA (5'-D(*DTP*DAP*DGP*DGP*DTP*DAP*DAP*DCP*DAP*DTP*DCP*DGP*DT)-3'), DNA (5'-D(*DAP*DAP*DCP*DGP*DAP*DTP*DAP*DTP*DTP*DAP*DCP*DCP*DT)-3'), ... (6 entities in total)
• Functional Keywords: alkylation repair, protein dna interaction, cross-linking, dioxygenase, dna repair, oxidoreductase-dna complex, oxidoreductase/dna
• Biological source: Escherichia coli K12
• Total number of polymer chains: 3
• Total formula weight: 30472.93

Authors

Yi, C.,Yang, C.-G.,He, C. (deposition date: 2007-12-09, release date: 2008-04-22, Last modification date: 2024-10-30)

Primary citation

Yang, C.-G.,Yi, C.,Duguid, E.M.,Sullivan, C.T.,Jian, X.,Rice, P.A.,He, C.
Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA
Nature, 452:961-965, 2008

PubMed Abstract: 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.

PubMed: 18432238
DOI: 10.1038/nature06889

Experimental method

X-RAY DIFFRACTION (1.65 Å)