1w7a: Difference between revisions
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==Overview== | ==Overview== | ||
MutS is the key protein of the Escherichia coli DNA mismatch repair, system. It recognizes mispaired and unpaired bases and has intrinsic, ATPase activity. ATP binding after mismatch recognition by MutS serves as, a switch that enables MutL binding and the subsequent initiation of, mismatch repair. However, the mechanism of this switch is poorly, understood. We have investigated the effects of ATP binding on the MutS, structure. Crystallographic studies of ATP-soaked crystals of MutS show a, trapped intermediate, with ATP in the nucleotide-binding site. Local, rearrangements of several residues around the nucleotide-binding site, suggest a movement of the two ATPase domains of the MutS dimer toward each, other. Analytical ultracentrifugation experiments confirm such a, rearrangement, ... | MutS is the key protein of the Escherichia coli DNA mismatch repair, system. It recognizes mispaired and unpaired bases and has intrinsic, ATPase activity. ATP binding after mismatch recognition by MutS serves as, a switch that enables MutL binding and the subsequent initiation of, mismatch repair. However, the mechanism of this switch is poorly, understood. We have investigated the effects of ATP binding on the MutS, structure. Crystallographic studies of ATP-soaked crystals of MutS show a, trapped intermediate, with ATP in the nucleotide-binding site. Local, rearrangements of several residues around the nucleotide-binding site, suggest a movement of the two ATPase domains of the MutS dimer toward each, other. Analytical ultracentrifugation experiments confirm such a, rearrangement, showing increased affinity between the ATPase domains upon, ATP binding and decreased affinity in the presence of ADP. Mutations of, specific residues in the nucleotide-binding domain reduce the dimer, affinity of the ATPase domains. In addition, ATP-induced release of DNA is, strongly reduced in these mutants, suggesting that the two activities are, coupled. Hence, it seems plausible that modulation of the affinity between, ATPase domains is the driving force for conformational changes in the MutS, dimer. These changes are driven by distinct amino acids in the, nucleotide-binding site and form the basis for long-range interactions, between the ATPase domains and DNA-binding domains and subsequent binding, of MutL and initiation of mismatch repair. | ||
==About this Structure== | ==About this Structure== | ||
1W7A is a | 1W7A is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with MG and ATP as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W7A OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: dna-binding]] | [[Category: dna-binding]] | ||
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Revision as of 16:18, 5 November 2007
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ATP BOUND MUTS
OverviewOverview
MutS is the key protein of the Escherichia coli DNA mismatch repair, system. It recognizes mispaired and unpaired bases and has intrinsic, ATPase activity. ATP binding after mismatch recognition by MutS serves as, a switch that enables MutL binding and the subsequent initiation of, mismatch repair. However, the mechanism of this switch is poorly, understood. We have investigated the effects of ATP binding on the MutS, structure. Crystallographic studies of ATP-soaked crystals of MutS show a, trapped intermediate, with ATP in the nucleotide-binding site. Local, rearrangements of several residues around the nucleotide-binding site, suggest a movement of the two ATPase domains of the MutS dimer toward each, other. Analytical ultracentrifugation experiments confirm such a, rearrangement, showing increased affinity between the ATPase domains upon, ATP binding and decreased affinity in the presence of ADP. Mutations of, specific residues in the nucleotide-binding domain reduce the dimer, affinity of the ATPase domains. In addition, ATP-induced release of DNA is, strongly reduced in these mutants, suggesting that the two activities are, coupled. Hence, it seems plausible that modulation of the affinity between, ATPase domains is the driving force for conformational changes in the MutS, dimer. These changes are driven by distinct amino acids in the, nucleotide-binding site and form the basis for long-range interactions, between the ATPase domains and DNA-binding domains and subsequent binding, of MutL and initiation of mismatch repair.
About this StructureAbout this Structure
1W7A is a Protein complex structure of sequences from Escherichia coli with MG and ATP as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
ATP increases the affinity between MutS ATPase domains. Implications for ATP hydrolysis and conformational changes., Lamers MH, Georgijevic D, Lebbink JH, Winterwerp HH, Agianian B, de Wind N, Sixma TK, J Biol Chem. 2004 Oct 15;279(42):43879-85. Epub 2004 Aug 4. PMID:15297450
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