FEBS Letters
Volume 583, Issue 12 , Pages 1901-1908, 18 June 2009

Identification of the nucleophilic factors and the productive complex for the editing reaction by leucyl-tRNA synthetase

Edited by Michael Ibba

  • Yohsuke Hagiwara

      Affiliations

    • Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8571, Japan
    • Center for Computational Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8571, Japan
    • ,
  • Osamu Nureki

      Affiliations

    • Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minatoku, Tokyo 108-8639, Japan
    • ,
  • Masaru Tateno

      Affiliations

    • Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8571, Japan
    • Center for Computational Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8571, Japan
    • Corresponding Author InformationCorresponding author. Address: Center for Computational Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8571, Japan. Fax: +81 29 853 6496.

Received 10 March 2009; received in revised form 12 May 2009; accepted 13 May 2009. published online 20 May 2009.

Abstract 

To ensure fidelity of translation, several aminoacyl-tRNA synthetases (aaRSs) possess editing capability to hydrolyse mis-aminoacylated tRNAs. In this report, based on our previously-modelled structure of leucyl-tRNA synthetase (LeuRS) complexed with valyl-tRNALeu, further structural modelling has been performed along with molecular dynamics simulations. This enabled the identification of the nucleophile, which is different from that suggested by the crystal structure of the LeuRS•Nva2AA complex. Our results revealed that the 3′ hydroxyl group of A76 acts as a “gate” to regulate the accessibility of the nucleophile; thus, the opening of the gate leads to the productive complex for the reaction.

Abbreviations: aaRS, aminoacyl-tRNA synthetase, LeuRS, leucyl-tRNA synthetase, ValRS, valyl-tRNA synthetase, ThrRS, threonyl-tRNA synthetase, MD, molecular dynamics, QM/MM, quantum mechanics/molecular mechanics, ES complex, enzyme•substrate complex

Keywords: Error-editing reaction, Nucleophile, Water, Molecular dynamics simulation, Quantum mechanics/molecular mechanics hybrid calculation

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PII: S0014-5793(09)00397-4

doi:10.1016/j.febslet.2009.05.026

FEBS Letters
Volume 583, Issue 12 , Pages 1901-1908, 18 June 2009

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