title: Transformation of MutL by ATP binding and hydrolysis: a switch in DNA mismatch repair.
abstract: The MutL DNA mismatch repair protein has recently been shown to be an ATPase and to belong to an emerging ATPase superfamily that includes DNA topoisomerase II and Hsp90. We report here the crystal structures of a 40 kDa ATPase fragment of E. coli MutL (LN40) complexed with a substrate analog, ADPnP, and with product ADP. More than 60 residues that are disordered in the apoprotein structure become ordered and contribute to both ADPnP binding and dimerization of LN40. Hydrolysis of ATP, signified by subsequent release of the gamma-phosphate, releases two key loops and leads to dissociation of the LN40 dimer. Dimerization of the LN40 region is required for and is the rate-limiting step in ATP hydrolysis by MutL. The ATPase activity of MutL is stimulated by DNA and likely acts as a switch to coordinate DNA mismatch repair.
authors: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: C
authors: C
authors: Ban
authors: M
authors: M
authors: Junop
authors: W
authors: W
authors: Yang
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000266:Adenylyl Imidodiphosphate / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D020137:Base Pair Mismatch / Q000502:physiology*; D018360:Crystallography, X-Ray; D004260:DNA Repair / Q000502:physiology*; D019281:Dimerization; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D006868:Hydrolysis; D008958:Models, Molecular; D000070956:MutL Proteins; D010455:Peptides / Q000378:metabolism / Q000502:physiology; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C074770:MutL protein, E coli; D010455:Peptides; D000266:Adenylyl Imidodiphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D000070956:MutL Proteins