title: Cooperative structural dynamics and a novel fidelity mechanism in histidyl-tRNA synthetases.
abstract: The crystal structure of the Staphylococcus aureus histidyl-tRNA synthetase apoprotein has been determined at 2.7 A resolution. Several important loops in the active site either become disordered or adopt very different conformations compared to their ligand-bound states. These include the histidine A motif (Arg257-Tyr262) that is essential for substrate recognition, a loop (Gly52-Lys62) that seems to control the communication between the histidine and ATP binding sites, the motif 2 loop (Glu114-Arg120) that binds ATP, and the insertion domain that is likely to bind tRNA. These ligand-induced structural changes are supported by fluorescence experiments, which also suggest highly cooperative dynamics. A dynamic and cooperative active site is most likely necessary for the proper functioning of the histidyl-tRNA synthetase, and suggests a novel mechanism for improving charging fidelity.
authors.affiliation: Department of Structural Biology, Department of Protein Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. xiayang_qiu-1@sbphrd.com
authors.forename: X
authors.initials: X
authors.lastname: Qiu
authors.forename: C A
authors.initials: CA
authors.lastname: Janson
authors.forename: M N
authors.initials: MN
authors.lastname: Blackburn
authors.forename: I K
authors.initials: IK
authors.lastname: Chhohan
authors.forename: M
authors.initials: M
authors.lastname: Hibbs
authors.forename: S S
authors.initials: SS
authors.lastname: Abdel-Meguid
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D019281:Dimerization; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D006643:Histidine-tRNA Ligase / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013211:Staphylococcus aureus / Q000201:enzymology; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
chemical_list: D008024:Ligands; D006639:Histidine; D014364:Tryptophan; D006643:Histidine-tRNA Ligase