3K0S

Crystal structure of E.coli DNA mismatch repair protein MutS, D693N mutant, in complex with GT mismatched DNA

Summary for 3K0S

• Entry DOI: 10.2210/pdb3k0s/pdb
• Related: 1E3M 1W7A
• 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*GP*TP*CP*AP*GP*CP*GP*TP*CP*CP*TP*AP*T)-3', 5'-D(*AP*TP*AP*GP*GP*AP*CP*GP*CP*TP*GP*AP*C*AP*CP*T*GP*GP*TP*GP*CP*TP*TP*GP*GP*CP*AP*GP*CP*T)-3', ... (5 entities in total)
• Functional Keywords: magnesium mutant, dna repair protein, protein-dna complex, atp-binding, dna damage, dna repair, dna-binding, nucleotide-binding, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Escherichia coli; More
• Total number of polymer chains: 4
• Total formula weight: 197836.41

Authors

Reumer, G.A.,Winterwerp, H.H.K.,Sixma, T.K. (deposition date: 2009-09-25, release date: 2010-02-16, Last modification date: 2023-09-06)

Primary citation

Lebbink, J.H.,Fish, A.,Reumer, A.,Natrajan, G.,Winterwerp, H.H.,Sixma, T.K.
Magnesium coordination controls the molecular switch function of DNA mismatch repair protein MutS.
J.Biol.Chem., 285:13131-13141, 2010

PubMed Abstract: The DNA mismatch repair protein MutS acts as a molecular switch. It toggles between ADP and ATP states and is regulated by mismatched DNA. This is analogous to G-protein switches and the regulation of their "on" and "off" states by guanine exchange factors. Although GDP release in monomeric GTPases is accelerated by guanine exchange factor-induced removal of magnesium from the catalytic site, we found that release of ADP from MutS is not influenced by the metal ion in this manner. Rather, ADP release is induced by the binding of mismatched DNA at the opposite end of the protein, a long-range allosteric response resembling the mechanism of activation of heterotrimeric GTPases. Magnesium influences switching in MutS by inducing faster and tighter ATP binding, allowing rapid downstream responses. MutS mutants with decreased affinity for the metal ion are impaired in fast switching and in vivo mismatch repair. Thus, the G-proteins and MutS conceptually employ the same efficient use of the high energy cofactor: slow hydrolysis in the absence of a signal and fast conversion to the active state when required.

PubMed: 20167596
DOI: 10.1074/jbc.M109.066001

Experimental method

X-RAY DIFFRACTION (2.2 Å)