Download MendeleyCooperative structural dynamics and a novel fidelity mechanism in histidyl-tRNA synthetases.
Qiu, X., Janson, C.A., Blackburn, M.N., Chhohan, I.K., Hibbs, M., Abdel-Meguid, S.S.(1999) Biochemistry 38: 12296-12304
- PubMed: 10493797
- DOI: https://doi.org/10.1021/bi990482v
- Primary Citation of Related Structures:
1QE0 - PubMed 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.
Organizational Affiliation:
Department of Structural Biology, Department of Protein Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. xiayang_qiu-1@sbphrd.com
