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

Amino acid selection by aminoacyl-tRNA synthetases requires efficient mecha nisms to avoid incorrect charging of the cognate tRNAs. A proofreading mech anism prevents Escherichia coli methionyl-tRNA synthetase (EcMet-RS) from a ctivating in vivo L-homocysteine, a natural competitor of L-methionine reco gnised by the enzyme. The crystal structure of the complex between EcMet-RS and L-methionine solved at 1.8 Angstrom resolution exhibits some conspicuo us differences with the recently published free enzyme structure. Thus, the methionine delta -sulphur atom replaces a water molecule H-bonded to Leu13 N and Tyr260O(eta) in the free enzyme. Rearrangements of aromatic residues enable the protein to form a hydrophobic pocket around the ligand side-chai n. The subsequent formation of an extended water molecule network contribut es to relative displacements, up to 3 Angstrom, of several domains of the p rotein. The structure of this complex supports a plausible mechanism for th e selection of L-methionine versus L-homocysteine and suggests the possibil ity of information transfer between the different functional domains of the enzyme. (C) 2001 Academic Press.