Histidyl-tRNA synthetase from Salmonella typhimurium. Specificity in the binding of histidine analogs

The topog. of the active site of histidyl-tRNA synthetase was investigated by detg. Ki values for a variety of structural analogs. of histidine, using the ATP-pyrophosphate exchange and tRNA aminoacylation reactions. Using these kinetic consts., was possible to have a measure of the relative binding affinity of the enzyme for the histidine analogues. The following conclusions were drawn: (a) the enzyme is stereospecific in the formation of aminoacyl-tRNA complexes, since the D-isomer of histidine does not influence the 2 reactions; (b) the CO2H group is not required for binding; (c) bulky derivs. of the CO2H group prevent the mols. from binding to the enzyme; (d) the NH2 group permits a good binding affinity; (e) the length of the ring side chain plays a very important role as point of attachment to the enzyme; and (f) the kinds of heteroatoms in the ring det. the inhibitory properties of the analogs. [on SciFinder(R)]