Selective inhibition of divergent seryl-tRNA synthetases by serine analogues.
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.
Ahel
Dragana
D
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
Slade
Dea
D
Mocibob
Marko
M
Söll
Dieter
D
Weygand-Durasevic
Ivana
I
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
D019843:Archaeal Proteins; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; C028002:serine hydroxamate; D012694:Serine; C429009:serine methyl ester; C503920:serinamide; D012714:Serine-tRNA Ligase