Cooperative structural dynamics and a novel fidelity mechanism in histidyl-tRNA synthetases

The crystal structure of the Staphylococcus aureus histidyl-tRNA synthetase apoprotein has been determined at 2.7 Angstrom resolution. Several importa nt loops in the active site either become disordered or adopt very differen t conformations compared to their ligand-bound states. These include the hi stidine 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 bind s ATP, and the insertion domain that is likely to bind tRNA. These ligand-i nduced 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-tR NA synthetase, and suggests a novel mechanism for improving charging fideli ty.