An organism-independent unified model for activity of orotate phosphoribosyltransferases for orotidine monophosphate synthesis

摘要

A unified model for orotate phosphoribosyltransferase-action has been developed describing the enzymatic synthesis of orotidine monophosphate, an important intermediate for nucleotide synthesis. The reaction, prevalent in micro-organisms, participates in the de nova nucleotide synthesis pathway, and is a popular target for inhibition to check the growth of Mycobacterium tuberculosis. Features of three enzymatic mechanisms, viz., ping-pong bi-bi mechanism, random kinetic mechanism and sequential kinetic mechanism were incorporated in the unified model to increase the range of successful applicability of the model and to make it organism independent, The model could successfully describe the kinetics of reaction for the reported data. Kinetics of the reaction with enzyme derived from Mycobacterium tuberculosis, Succhurornyces cerevisiue, Salmonella typhimurium and Plasmodium falcipuntrn was tested and the unified model was found to be valid with a change in the organism from which the enzyme has been derived. The model can serve as a reliable model to describe the kinetics of the reaction with enzyme derived from new organisms without having to do the mechanistic determination owing to organism independent nature of the model. (C) 2015 Elsevier Ltd. All rights reserved.