title: How glutaminyl-tRNA synthetase selects glutamine.
abstract: BACKGROUND
  Aminoacyl-tRNA synthetases covalently link a specific amino acid to the correct tRNA. The fidelity of this reaction is essential for accurate protein synthesis. Each synthetase has a specific molecular mechanism to distinguish the correct pair of substrates from the pool of amino acids and isologous tRNA molecules. In the case of glutaminyl-tRNA synthetase (GlnRS) the prior binding of tRNA is required for activation of glutamine by ATP. A complete understanding of amino acid specificity in GlnRS requires the determination of the structure of the synthetase with both tRNA and substrates bound.
  
  
  RESULTS
  A stable glutaminly-adenylate analog, which inhibits GlnRS with a Ki of 1.32 microM, was synthesized and cocrystallized with GlnRS and tRNA2Gln. The crystal structure of this ternary complex has been refined at 2.4 A resolution and shows the interactions made between glutamine and its binding site.
  
  
  CONCLUSIONS
  To select against glutamic acid or glutamate, both hydrogen atoms of the nitrogen of the glutamine sidechain are recognized. The hydroxyl group of Tyr211 and a water molecule are responsible for this recognition; both are obligate hydrogen-bond acceptors due to a network of interacting sidechains and water molecules. The prior binding of tRNAGln that is required for amino acid activation may result from the terminal nucleotide, A76, packing against and orienting Tyr211, which forms part of the amino acid binding site.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, PO Box 208114, New Haven, CT 06520-8114, USA.
authors.forename: V L
authors.initials: VL
authors.lastname: Rath
authors.forename: L F
authors.initials: LF
authors.lastname: Silvian
authors.forename: B
authors.initials: B
authors.lastname: Beijer
authors.forename: B S
authors.initials: BS
authors.lastname: Sproat
authors.forename: T A
authors.initials: TA
authors.lastname: Steitz
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry*; D001665:Binding Sites / Q000502:physiology; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology; D005973:Glutamine / Q000031:analogs & derivatives / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D012351:RNA, Transfer, Gln / Q000737:chemistry*; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D012351:RNA, Transfer, Gln; D005973:Glutamine; D000255:Adenosine Triphosphate; D000604:Amino Acyl-tRNA Synthetases; C020659:glutaminyl-tRNA synthetase