Download MendeleyHow methionyl-tRNA synthetase creates its amino acid recognition pocket upon L-methionine binding.
Serre, L., Verdon, G., Choinowski, T., Hervouet, N., Risler, J.L., Zelwer, C.(2001) J Mol Biol 306: 863-876
- PubMed: 11243794
- DOI: https://doi.org/10.1006/jmbi.2001.4408
- Primary Citation of Related Structures:
1F4L - PubMed 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 A 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 A, 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.
Organizational Affiliation:
Centre de Biophysique Moléculaire, Centre National de la Recherche Scientifique, rue Charles Sadron, Orléans Cedex 2, 45071, France.
