1MWJ

Crystal Structure of a MUG-DNA pseudo substrate complex

1MWJ の概要

• エントリーDOI: 10.2210/pdb1mwj/pdb
• 関連するPDBエントリー: 1MUG
• 分子名称: 5'-D(*CP*GP*CP*GP*A*GP*(DU)P*TP*CP*GP*CP*G)-3', G/U mismatch-specific DNA glycosylase (3 entities in total)
• 機能のキーワード: rossmann fold, non-hydrolysable dna-complex, uracil recognition., hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm : P0A9H1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22361.72

構造登録者

Barrett, T.E.,Scharer, O.,Savva, R.,Brown, T.,Jiricny, J.,Verdine, G.L.,Pearl, L.H. (登録日: 2002-09-30, 公開日: 2002-10-11, 最終更新日: 2026-03-04)

主引用文献

Barrett, T.E.,Scharer, O.,Savva, R.,Brown, T.,Jiricny, J.,Verdine, G.L.,Pearl, L.H.
Crystal Structure of a thwarted mismatch glycosylase DNA repair complex
Embo J., 18:6599-6609, 1999

PubMed Abstract: The bacterial mismatch-specific uracil-DNA glycosylase (MUG) and eukaryotic thymine-DNA glycosylase (TDG) enzymes form a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches. Despite low sequence homology, the MUG/TDG enzymes are structurally related to the uracil-DNA glycosylase enzymes, but have a very different mechanism for substrate recognition. We have now determined the crystal structure of the Escherichia coli MUG enzyme complexed with an oligonucleotide containing a non-hydrolysable deoxyuridine analogue mismatched with guanine, providing the first structure of an intact substrate-nucleotide productively bound to a hydrolytic DNA glycosylase. The structure of this complex explains the preference for G:U over G:T mispairs, and reveals an essentially non-specific pyrimidine-binding pocket that allows MUG/TDG enzymes to excise the alkylated base, 3, N(4)-ethenocytosine. Together with structures for the free enzyme and for an abasic-DNA product complex, the MUG-substrate analogue complex reveals the conformational changes accompanying the catalytic cycle of substrate binding, base excision and product release.

PubMed: 10581234
DOI: 10.1093/emboj/18.23.6599

実験手法

X-RAY DIFFRACTION (2.85 Å)