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.
Serre
L
L
Centre de Biophysique Moléculaire, Centre National de la Recherche Scientifique, rue Charles Sadron, Orléans Cedex 2, 45071, France.
Verdon
G
G
Choinowski
T
T
Hervouet
N
N
Risler
J L
JL
Zelwer
C
C
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