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Accueil > Publications > Recherche par années > Années 2000 > 2001

Serre, L ; Verdon, G ; Choinowski, T ; Hervouet, N ; Risler, JL ; Zelwer, C

How methionyl-tRNA synthetase creates its amino acid recognition pocket upon L-methionine binding

Journal of Molecular Biology 306 (4) 863-876

par Administrateur - publié le

Abstract :

Amino acid selection by aminoacyl-tRNA synthetases requires efficient mechanisms to avoid incorrect charging of the cognate tRNAs. A proofreading mechanism prevents Escherichia coli methionyl-tRNA synthetase (EcMet-RS) from activating in vivo L-homocysteine, a natural competitor of L-methionine recognised by the enzyme. The crystal structure of the complex between EcMet-RS and L-methionine solved at 1.8 Angstrom resolution exhibits some conspicuous differences with the recently published free enzyme structure. Thus, the methionine delta -sulphur atom replaces a water molecule H-bonded to Leu13N and Tyr260O(eta) in the free enzyme. Rearrangements of aromatic residues enable the protein to form a hydrophobic pocket around the ligand side-chain. The subsequent formation of an extended water molecule network contributes to relative displacements, up to 3 Angstrom, of several domains of the protein. The structure of this complex supports a plausible mechanism for the selection of L-methionine versus L-homocysteine and suggests the possibility of information transfer between the different functional domains of the enzyme. (C) 2001 Academic Press.