Leaving group activation and pyrophosphate ionic state at the catalytic site of Plasmodium falciparum orotate phosphoribosyltransferase

Isotope-edited Fourier transform infrared (FTIR) spectrometry complemented by homology modeling and quantum chemical calculations are used for analyzing the orotate hydrogen-bond network for Plasmodium falciparum orotate phosphoribosyltransferase (PfOPRT). The results have provided reaction coordinate information for the PfOPRT-catalyzed orotidine 5E-monophosphate (OMP) and transition-state analysis has supported a dianionic orotic acid (OA) leaving group.