Steve Ealick's Research Group

Leishmania donovani UMP Synthase

PDB file:



The final two steps of de novo uridine 5′-monophosphate (UMP) biosynthesis are catalyzed by orotate phosphoribosyltransferase (OPRT) and orotidine 5′-monophosphate decarboxylase (OMPDC).  In most prokaryotes and simple eukaryotes these two enzymes are encoded by separate genes, while in mammals they are expressed as a bifunctional gene product called UMP synthase (UMPS), with OPRT at the N-terminus and OMPDC at the C-terminus.  Leishmania and some closely related organisms also express a bifunctional enzyme for these two steps, but the domain order is reversed relative to mammalian UMPS. The structure of Leishmania donovani UMPS (LdUMPS) was determined by molecular replacement using LdOMPDC and C. diphtheriae OPRT (PDB ID 2P1Z) as search models.

The LdUMPS protomer consists of an OMPDC domain (right) and an OPRT domain (left). When assembled into a dimer (below), the protomers are not superimposable because of difference in relative positioning of the domains.


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The two OMPDC domains in the LdUMPS structure form a tight dimer (left)that is homologous to that seen in the monofunctional LdOMPDC; however, the quaternary form is a tetramer (right). The dimeric LdOMPDC and LdOPRT functional domains in the tetramer are consistent with those observed in homologous structures of the monofunctional species. UMP is shown in ball-and-stick.

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The OMPDC domain was shown on the LdOMPDC page. Probably due to the high concentration of UMP used in the experiment, UMP was found bound in the OMP site in the ORT domain.

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French JB, Yates PA, Soysa DR, Boitz JM, Carter NS, Chang B, Ullman B, and Ealick SE. The Leishmania donovani UMP synthase is essential for promastigote viability and has an unusual tetrameric structure that exhibits substrate-controlled oligomerization. J. Biol. Chem. 296:20930-20941 (2011). PubMed

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