title: 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.
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Cha
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Chang Hwa
authors.initials: CH
authors.lastname: Jo
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Ahreum
authors.initials: A
authors.lastname: Han
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea. Electronic address: chahong@korea.ac.kr.
authors.forename: Kwang Yeon
authors.initials: KY
authors.lastname: Hwang
mesh_terms: D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000737:chemistry; D001120:Arginine / Q000737:chemistry; D001126:Arginine-tRNA Ligase / Q000737:chemistry*; D002172:Canavanine / Q000737:chemistry; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D040681:Structural Homology, Protein
chemical_list: D001051:Apoenzymes; D002172:Canavanine; D001120:Arginine; D001126:Arginine-tRNA Ligase
keywords: Arginyl-tRNA synthetase; Enzyme Commission number (6.1.1.19); Rossmann fold; l-Arginine; l-Canavanine; tRNA(Arg)