1WBB

Crystal structure of E. coli DNA mismatch repair enzyme MutS, E38A mutant, in complex with a G.T mismatch

1WBB の概要

• エントリーDOI: 10.2210/pdb1wbb/pdb
• 関連するPDBエントリー: 1E3M 1NG9 1OH5 1OH6 1OH7 1OH8 1W7A 1WB9 1WBD
• 分子名称: DNA MISMATCH REPAIR PROTEIN MUTS, 5'-D(*AP*GP*CP*TP*GP*CP*CP*AP*GP*GP *CP*AP*CP*CP*AP*GP*TP*G)-3', 5'-D(*AP*CP*TP*GP*GP*TP*GP*CP*TP*TP *GP*GP*CP*AP*GP*CP*T)-3', ... (6 entities in total)
• 機能のキーワード: dna-binding, atp-binding, dna binding, dna repair, mismatch recognition
• 由来する生物種: ESCHERICHIA COLI
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 190305.11

構造登録者

Natrajan, G.,Georgijevic, D.,Lebbink, J.H.G.,Winterwerp, H.H.K.,de Wind, N.,Sixma, T.K. (登録日: 2004-10-31, 公開日: 2006-01-18, 最終更新日: 2023-12-13)

主引用文献

Lebbink, J.H.G.,Georgijevic, D.,Natrajan, G.,Fish, A.,Winterwerp, H.H.K.,Sixma, T.K.,De Wind, N.
Dual Role of Muts Glutamate 38 in DNA Mismatch Discrimination and in the Authorization of Repair.
Embo J., 25:409-, 2006

PubMed Abstract: MutS plays a critical role in DNA mismatch repair in Escherichia coli by binding to mismatches and initiating repair in an ATP-dependent manner. Mutational analysis of a highly conserved glutamate, Glu38, has revealed its role in mismatch recognition by enabling MutS to discriminate between homoduplex and mismatched DNA. Crystal structures of MutS have shown that Glu38 forms a hydrogen bond to one of the mismatched bases. In this study, we have analyzed the crystal structures, DNA binding and the response to ATP binding of three Glu38 mutants. While confirming the role of the negative charge in initial discrimination, we show that in vivo mismatch repair can proceed even when discrimination is low. We demonstrate that the formation of a hydrogen bond by residue 38 to the mismatched base authorizes repair by inducing intramolecular signaling, which results in the inhibition of rapid hydrolysis of distally bound ATP. This allows formation of the stable MutS-ATP-DNA clamp, a key intermediate in triggering downstream repair events.

PubMed: 16407973
DOI: 10.1038/SJ.EMBOJ.7600936

実験手法

X-RAY DIFFRACTION (2.5 Å)