Small molecules: big players in the evolution of protein synthesis.
The aminoacyl-tRNA synthetases (aaRSs) are responsible for selecting specific amino acids for protein synthesis, and this essential role in translation has garnered them much attention as targets for novel antimicrobials. Understanding how the aaRSs evolved efficient substrate selection offers a potential route to develop useful inhibitors of microbial protein synthesis. Here, we discuss discrimination of small molecules by aaRSs, and how the evolutionary divergence of these mechanisms offers a means to target inhibitors against these essential microbial enzymes.
Ataide
Sandro F
SF
Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, USA.
Ibba
Michael
M
D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D019020:Directed Molecular Evolution / Q000379:methods / Q000639:trends; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D006801:Humans; D011500:Protein Synthesis Inhibitors / Q000138:chemical synthesis*
D000890:Anti-Infective Agents; D011500:Protein Synthesis Inhibitors; D000604:Amino Acyl-tRNA Synthetases