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.
