1hlw

STRUCTURE OF THE H122A MUTANT OF THE NUCLEOSIDE DIPHOSPHATE KINASE

spinqualitylabelsall models 1hlw, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1hlw is a 1 chain structure with sequence from Atcc 11735. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 1b4s Activity: Nucleoside-diphosphate kinase, with EC number 2.7.4.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 We have explored the ability of a nucleoside diphosphate kinase (NDPK) mutant in which the nucleophilic histidine has been replaced by glycine (H122G) to transfer phosphate from ATP to alcohols of varying pK(a), size, shape, and polarity. This cavity mutant does indeed act as a primitive alcohol kinase. The rate of its phosphoryl transfer to alcohols varies considerably, with values spanning a DeltaDeltaG(double dagger) range of 4 kcal/mol, whereas the alcohols have very similar intrinsic reactivities. Analysis of these results suggests that the ability to carry out phosphoryl transfer within the cavity is not a simple function of being small enough to enter the cavity, but rather is a complex function of steric, solvation, entropic, van der Waals packing, and electrostatic properties of the alcohol. In addition, large differences are observed between the reactivities of alcohols within the nucleophile cavity of H122G and the reactivities of the same alcohols within the nucleophile cavity of H122A, a mutant NDPK that differs from H122G by a single methyl group within the cavity. The crystal structures of the two cavity mutants are very similar to one another and to wild-type NDPK, providing no evidence for a structurally perturbed active site. The differences in reactivity between the two mutant proteins illustrate a fundamental limitation of energetic analysis from site-directed mutagenesis: although removal of a side chain is generally considered to be a conservative change, the energetic effects of any given mutation are inextricably linked to the molecular properties of the created cavity and the surrounding protein environment. Chemical rescue of phosphoryl transfer in a cavity mutant: a cautionary tale for site-directed mutagenesis.,Admiraal SJ, Meyer P, Schneider B, Deville-Bonne D, Janin J, Herschlag D Biochemistry. 2001 Jan 16;40(2):403-13. PMID:11148034 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nucleoside diphosphate kinase 3D structures

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