title: Structural basis for double-sieve discrimination of L-valine from L-isoleucine and L-threonine by the complex of tRNA(Val) and valyl-tRNA synthetase.
abstract: Valyl-tRNA synthetase (ValRS) strictly discriminates the cognate L-valine from the larger L-isoleucine and the isosteric L-threonine by the tRNA-dependent "double sieve" mechanism. In this study, we determined the 2.9 A crystal structure of a complex of Thermus thermophilus ValRS, tRNA(Val), and an analog of the Val-adenylate intermediate. The analog is bound in a pocket, where Pro(41) allows accommodation of the Val and Thr moieties but precludes the Ile moiety (the first sieve), on the aminoacylation domain. The editing domain, which hydrolyzes incorrectly synthesized Thr-tRNA(Val), is bound to the 3' adenosine of tRNA(Val). A contiguous pocket was found to accommodate the Thr moiety, but not the Val moiety (the second sieve). Furthermore, another Thr binding pocket for Thr-adenylate hydrolysis was suggested on the editing domain.
authors: Department of Biophysics and Biochemistry Graduate School of Science The University of Tokyo 7-3-1 Hongo Bunkyo-ku, 113-0033, Tokyo, Japan.
authors: S
authors: S
authors: Fukai
authors: O
authors: O
authors: Nureki
authors: S
authors: S
authors: Sekine
authors: A
authors: A
authors: Shimada
authors: J
authors: J
authors: Tao
authors: D G
authors: DG
authors: Vassylyev
authors: S
authors: S
authors: Yokoyama
mesh_terms: D000241:Adenosine / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006868:Hydrolysis; D007532:Isoleucine / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012366:RNA, Transfer, Val / Q000737:chemistry* / Q000378:metabolism; D016963:Thermus thermophilus / Q000737:chemistry; D013912:Threonine / Q000737:chemistry*; D014633:Valine / Q000737:chemistry*; D014637:Valine-tRNA Ligase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D012366:RNA, Transfer, Val; D007532:Isoleucine; D013912:Threonine; D011392:Proline; D014637:Valine-tRNA Ligase; D014633:Valine; D000241:Adenosine