3QW3

Structure of Leishmania donovani OMP decarboxylase

3QW3 の概要

• エントリーDOI: 10.2210/pdb3qw3/pdb
• 分子名称: Orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative (Ompdcase-oprtase, putative), SULFATE ION (3 entities in total)
• 機能のキーワード: orotidine monophosphate decarboxylase, transferase, lyase
• 由来する生物種: Leishmania infantum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55308.67

構造登録者

French, J.B.,Ealick, S.E. (登録日: 2011-02-26, 公開日: 2011-04-20, 最終更新日: 2024-02-21)

主引用文献

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

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: 21507942
DOI: 10.1074/jbc.M111.228213

実験手法

X-RAY DIFFRACTION (1.7 Å)