1nhh

Crystal structure of N-terminal 40KD MutL protein (LN40) complex with ADPnP and one Rubidium

spinqualitylabelsall models 1nhh, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1nhh is a 1 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: ANP, EDO, MG, RB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MUTL_ECOLI This protein is involved in the repair of mismatches in DNA. It is required for dam-dependent methyl-directed DNA mismatch repair. May act as a "molecular matchmaker", a protein that promotes the formation of a stable complex between two or more DNA-binding proteins in an ATP-dependent manner without itself being part of the final effector complex. The ATPase activity of MutL is stimulated by DNA. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The GHKL phosphotransferase superfamily, characterized by four sequence motifs that form the ATP-binding site, consists of the ATPase domains of type II DNA topoisomerases, Hsp90, and MutL, and bacterial and mitochondrial protein kinases. In addition to a magnesium ion, which is essential for catalysis, a potassium ion bound adjacent to the triphosphate moiety of ATP in a rat mitochondrial protein kinase, BCK (branched-chain alpha-ketoacid dehydrogenase kinase), has been shown to be indispensable for nucleotide binding and hydrolysis. Using X-ray crystallographic, biochemical, and genetic analyses, we find that the monovalent cation-binding site is conserved in MutL, but both Na(+) and K(+) support the MutL ATPase activity. When Ala100 of MutL is substituted by proline, mimicking the K(+)-binding environment in BCK, the mutant MutL protein becomes exclusively dependent on Na(+) for the ATPase activity. The coordination of this Na(+) ion is identical to that of the K(+) ion in BCK and involves four carbonyl oxygen atoms emanating from the hinges of the ATP lid and a non-bridging oxygen of the bound nucleotide. A similar monovalent cation-binding site is found in DNA gyrase with additional coordination by a serine side chain. The conserved and protein-specific monovalent cation-binding site is unique to the GHKL superfamily and probably essential for both ATPase and kinase activity. Dependence on different monovalent cations for catalysis may be exploited for future drug design specifically targeting each individual member of the GHKL superfamily. Monovalent cation dependence and preference of GHKL ATPases and kinases.,Hu X, Machius M, Yang W FEBS Lett. 2003 Jun 5;544(1-3):268-73. PMID:12782329 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA mismatch repair protein 3D structures

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