3QW3
Structure of Leishmania donovani OMP decarboxylase
Summary for 3QW3
| Entry DOI | 10.2210/pdb3qw3/pdb |
| Descriptor | Orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative (Ompdcase-oprtase, putative), SULFATE ION (3 entities in total) |
| Functional Keywords | orotidine monophosphate decarboxylase, transferase, lyase |
| Biological source | Leishmania infantum |
| Total number of polymer chains | 2 |
| Total formula weight | 55308.67 |
| Authors | French, J.B.,Ealick, S.E. (deposition date: 2011-02-26, release date: 2011-04-20, Last modification date: 2024-02-21) |
| Primary citation | French, J.B.,Yates, P.A.,Soysa, D.R.,Boitz, J.M.,Carter, N.S.,Chang, B.,Ullman, B.,Ealick, S.E. The Leishmania donovani UMP synthase is essential for promastigote viability and has an unusual tetrameric structure that exhibits substrate-controlled oligomerization. J.Biol.Chem., 286:20930-20941, 2011 Cited by PubMed Abstract: 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, whereas 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. In this work we demonstrate that L. donovani UMPS (LdUMPS) is an essential enzyme in promastigotes and that it is sequestered in the parasite glycosome. We also present the crystal structure of the LdUMPS in complex with its product, UMP. This structure reveals an unusual tetramer with two head to head and two tail to tail interactions, resulting in two dimeric OMPDC and two dimeric OPRT functional domains. In addition, we provide structural and biochemical evidence that oligomerization of LdUMPS is controlled by product binding at the OPRT active site. We propose a model for the assembly of the catalytically relevant LdUMPS tetramer and discuss the implications for the structure of mammalian UMPS. PubMed: 21507942DOI: 10.1074/jbc.M111.228213 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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