title: Selective inhibition of divergent seryl-tRNA synthetases by serine analogues.
abstract: Seryl-tRNA synthetases (SerRSs) fall into two distinct evolutionary groups of enzymes, bacterial and methanogenic. These two types of SerRSs display only minimal sequence similarity, primarily within the class II conserved motifs, and possess distinct modes of tRNA(Ser) recognition. In order to determine whether the two types of SerRSs also differ in their recognition of the serine substrate, we compared the sensitivity of the representative methanogenic and bacterial-type SerRSs to serine hydroxamate and two previously unidentified inhibitors, serinamide and serine methyl ester. Our kinetic data showed selective inhibition of the methanogenic SerRS by serinamide, suggesting a lack of mechanistic uniformity in serine recognition between the evolutionarily distinct SerRSs.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
authors.forename: Dragana
authors.initials: D
authors.lastname: Ahel
authors.forename: Dea
authors.initials: D
authors.lastname: Slade
authors.forename: Marko
authors.initials: M
authors.lastname: Mocibob
authors.forename: Dieter
authors.initials: D
authors.lastname: Söll
authors.forename: Ivana
authors.initials: I
authors.lastname: Weygand-Durasevic
mesh_terms: D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000037:antagonists & inhibitors; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D017021:Methanosarcina barkeri / Q000201:enzymology; D008969:Molecular Sequence Data; D010802:Phylogeny; D012694:Serine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012714:Serine-tRNA Ligase / Q000037:antagonists & inhibitors* / Q000145:classification; D013379:Substrate Specificity
chemical_list: D019843:Archaeal Proteins; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; C028002:serine hydroxamate; D012694:Serine; C429009:serine methyl ester; C503920:serinamide; D012714:Serine-tRNA Ligase