Identification of the nucleophilic factors and the productive complex for the editing reaction by leucyl-tRNA synthetase.
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-tRNA(Leu), 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.
Hagiwara
Yohsuke
Y
Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Nureki
Osamu
O
Tateno
Masaru
M
D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D007935:Leucine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D017393:RNA Editing; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D016808:Tetrahymena thermophila / Q000201:enzymology; D013816:Thermodynamics
D012346:RNA, Transfer, Amino Acyl; D007935:Leucine-tRNA Ligase