Cell. 1998 Nov 13;95(4):541-52.

Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis.

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Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

MutL and its homologs are essential for DNA mismatch repair. Mutations in genes encoding human homologs of MutL cause multiorgan cancer susceptibility. We have determined the crystal structure of a 40 kDa N-terminal fragment of E. coli MutL that retains all of the conserved residues in the MutL family. The structure of MutL is homologous to that of an ATPase-containing fragment of DNA gyrase. We have demonstrated that MutL binds and hydrolyzes ATP to ADP and Pi. Mutations in the MutL family that cause deficiencies in DNA mismatch repair and a predisposition to cancer mainly occur in the putative ATP-binding site. We provide evidence that the flexible, yet conserved, loops surrounding this ATP-binding site undergo conformational changes upon ATP hydrolysis thereby modulating interactions between MutL and other components of the repair machinery.

PMID:: 9827806; [PubMed - indexed for MEDLINE]

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PDB/1BKN

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Cited by 66 PubMed Central articles

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Structures reported by this article

Crystal Structure Of An N-Terminal 40kd Fragment Of E. Coli Dna Mismatch Repair Protein Mutl

PDB: 1BKN

Source: Escherichia coli K-12

Method: X-Ray Diffraction

Resolution: 2.9 Å

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