3BU0

crystal structure of human ABH2 cross-linked to dsDNA with cofactors

Summary for 3BU0

• Entry DOI: 10.2210/pdb3bu0/pdb
• Related: 2FD8 2IUW 3BTX 3BTY 3BTZ 3BUC
• Descriptor: Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2, DNA (5'-D(*CP*TP*GP*TP*AP*TP*(2YR)P*AP*TP*TP*GP*CP*G)-3'), DNA (5'-D(*DTP*DCP*DGP*DCP*DAP*DAP*DTP*DAP*DAP*DTP*DAP*DCP*DA)-3'), ... (6 entities in total)
• Functional Keywords: protein/dna interaction, human dioxygenase, dna repair, cross-link, dna damage, iron, metal-binding, nucleus, oxidoreductase, oxidoreductase-dna complex, oxidoreductase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q6NS38
• Total number of polymer chains: 3
• Total formula weight: 31226.70

Authors

Yang, C.-G.,Yi, C.,He, C. (deposition date: 2007-12-31, release date: 2008-04-22, Last modification date: 2021-10-20)

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 (2.5 Å)