The crystal structure of arginyl-tRNA synthetase from Homo sapiens

Abstract

Arginyl-tRNA synthetase (ArgRS) is a tRNA-binding protein that catalyzes the esterification of L-arginine to its cognate tRNA. L-Canavanine, a structural analog of L-arginine, has recently been studied as an anticancer agent. Here, we determined the crystal structures of the apo, L-arginine-complexed, and L-canavanine-complexed forms of the cytoplasmic free isoform of human ArgRS (hArgRS). Similar interactions were formed upon binding to L-canavanine or L-arginine, but the interaction between Tyr312 and the oxygen of the oxyguanidino group was a little bit different. Detailed conformational changes that occur upon substrate binding were explained. The hArgRS structure was also compared with previously reported homologue structures. The results presented here may provide a basis for the design of new anticancer drugs, such as L-canavanine analogs.

Keywords: Arginyl-tRNA synthetase; Enzyme Commission number (6.1.1.19); Rossmann fold; l-Arginine; l-Canavanine; tRNA(Arg).