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

Shuya Fukai, Osamu Nureki, Shun ichi Sekine, Atsushi Shimada, Jianshi Tao, Dmitry G. Vassylyev, Shigeyuki Yokoyama

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230 Citations (Scopus)

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 Å 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 Pro41 allows accommodation of the Val and Thr moieties but precludes the lle 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.

Original languageEnglish
Pages (from-to)793-803
Number of pages11
JournalCell
Volume103
Issue number5
DOIs
Publication statusPublished - Nov 22 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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