The crystal structure of arginyl-tRNA synthetase from Homo sapiens.

Hyun Sook Kim, So Young Cha, Chang Hwa Jo, Ahreum Han, Kwang Yeon Hwang

Index: FEBS Lett. 588(14) , 2328-34, (2014)

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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.Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.