OMP decarboxylase : the reaction mechanism and the binding of an isosteric inhibitor /

Abstract

Orotidylate decarboxylase (ODCase) is the final enzyme in the de novo biosynthetic pathway of pyrimidine biosynthesis. The chemical mechanism by which ODCase catalyzes the formation of uridylate (UMP) to orotidylate (OMP) is not yet apparent since it follows no common decarboxylation routes. Our group has suggested a model for this decarboxylation that involves proton donation to the transition state in a concerted ylide/zwitterions mechanism. Yeast ODCase was purified of any contaminating proteins. Complete synthesis and characterization of transition-analogues was performed which act and were used as inhibitors to explore the enzyme active site. IH NMR of spectroscopy of ODCase in complex with 6-thiocarboxamidoruidine-5'monophosphate reveals a new downfield signal, possible identifying hydrogen bonds between the enzyme and the inhibitor. Our proposed catalytic mechanism and the results obtained from the experiment are to be discussed in this thesis.