3BTY

Crystal structure of human ABH2 bound to dsDNA containing 1meA through cross-linking away from active site

3BTY の概要

• エントリーDOI: 10.2210/pdb3bty/pdb
• 関連するPDBエントリー: 2FD8 2IUW 3BTX 3BTZ 3BU0 3BUC
• 分子名称: DNA (5'-D(*DCP*DTP*DGP*DTP*DAP*DTP*(MA7)P*DAP*DCP*DTP*DGP*DCP*DG)-3'), DNA (5'-D(*DTP*DCP*DGP*DCP*DAP*DGP*DTP*DTP*DAP*DTP*DAP*DCP*DA)-3'), Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2, ... (5 entities in total)
• 機能のキーワード: protein/dna interaction, human dioxygenase, dna repair, cross-linking, dna damage, iron, metal-binding, nucleus, oxidoreductase, oxidoreductase-dna complex, oxidoreductase/dna
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q6NS38
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 31144.80

構造登録者

Yang, C.-G.,Yi, C.,He, C. (登録日: 2007-12-31, 公開日: 2008-04-22, 最終更新日: 2024-10-09)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.35 Å)