1wbd
From Proteopedia
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==Overview== | ==Overview== | ||
| - | MutS plays a critical role in DNA mismatch repair in Escherichia coli by | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Georgijevic, D.]] | [[Category: Georgijevic, D.]] | ||
| - | [[Category: Lebbink, J | + | [[Category: Lebbink, J H.G.]] |
[[Category: Natrajan, G.]] | [[Category: Natrajan, G.]] | ||
| - | [[Category: Sixma, T | + | [[Category: Sixma, T K.]] |
| - | [[Category: Wind, N | + | [[Category: Wind, N De.]] |
| - | [[Category: Winterwerp, H | + | [[Category: Winterwerp, H H.K.]] |
[[Category: ADP]] | [[Category: ADP]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: mismatch recognition]] | [[Category: mismatch recognition]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:42:28 2008'' |
Revision as of 13:42, 21 February 2008
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CRYSTAL STRUCTURE OF E. COLI DNA MISMATCH REPAIR ENZYME MUTS, E38Q MUTANT, IN COMPLEX WITH A G.T MISMATCH
Overview
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.
About this Structure
1WBD is a Protein complex structure of sequences from Escherichia coli with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Dual role of MutS glutamate 38 in DNA mismatch discrimination and in the authorization of repair., Lebbink JH, Georgijevic D, Natrajan G, Fish A, Winterwerp HH, Sixma TK, de Wind N, EMBO J. 2006 Jan 25;25(2):409-19. Epub 2006 Jan 12. PMID:16407973
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