1WBD

Crystal structure of E. coli DNA mismatch repair enzyme MutS, E38Q mutant, in complex with a G.T mismatch

Summary for 1WBD

• Entry DOI: 10.2210/pdb1wbd/pdb
• Related: 1E3M 1NG9 1OH5 1OH6 1OH7 1OH8 1W7A 1WB9 1WBB
• Descriptor: 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)
• Functional Keywords: dna-binding, atp-binding, dna binding, dna repair, mismatch recognition
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 4
• Total formula weight: 190419.22

Authors

Natrajan, G.,Georgijevic, D.,Lebbink, J.H.G.,Winterwerp, H.H.K.,de Wind, N.,Sixma, T.K. (deposition date: 2004-10-31, release date: 2006-01-18, Last modification date: 2023-12-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)