title: Mutational analysis of conserved residues of the beta-subunit of human farnesyl:protein transferase.
abstract: The roles of 11 conserved amino acids of the beta-subunit of human farnesyl:protein transferase (FTase) were examined by performing kinetic and biochemical analyses of site-directed mutants. This biochemical information along with the x-ray crystal structure of rat FTase indicates that residues His-248, Arg-291, Lys-294, and Trp-303 are involved with binding and utilization of the substrate farnesyl diphosphate. Our data confirm structural evidence that amino acids Cys-299, Asp-297, and His-362 are ligands for the essential Zn2+ ion and suggest that Asp-359 may also play a role in Zn2+ binding. Additionally, we demonstrate that Arg-202 is important for binding the essential C-terminal carboxylate of the protein substrate.
authors.affiliation: Department of Cancer Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Kral
authors.forename: R E
authors.initials: RE
authors.lastname: Diehl
authors.forename: S J
authors.initials: SJ
authors.lastname: deSolms
authors.forename: T M
authors.initials: TM
authors.lastname: Williams
authors.forename: N E
authors.initials: NE
authors.lastname: Kohl
authors.forename: C A
authors.initials: CA
authors.lastname: Omer
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine; D001483:Base Sequence; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D051231:Farnesyltranstransferase; D006639:Histidine; D006801:Humans; D007700:Kinetics; D008239:Lysine; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014364:Tryptophan
chemical_list: D046911:Macromolecular Substances; D011994:Recombinant Proteins; D006639:Histidine; D014364:Tryptophan; D001120:Arginine; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D008239:Lysine