How methionyl-tRNA synthetase creates its amino acid recognition pocket upon L-methionine binding.
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.
Centre de Biophysique Moléculaire, Centre National de la Recherche Scientifique, rue Charles Sadron, Orléans Cedex 2, 45071, France.
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Serre
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Verdon
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Choinowski
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Hervouet
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Risler
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Zelwer
D000494:Allosteric Regulation; D000495:Allosteric Site; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D003460:Crystallization; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology*; D006710:Homocysteine / Q000378:metabolism; D006860:Hydrogen Bonding; D008715:Methionine / Q000737:chemistry / Q000378:metabolism*; D008718:Methionine-tRNA Ligase / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry / Q000378:metabolism
D014867:Water; D006710:Homocysteine; D008715:Methionine; D008718:Methionine-tRNA Ligase