3QW3

Structure of Leishmania donovani OMP decarboxylase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

The Leishmania donovani UMP synthase is essential for promastigote viability and has an unusual tetrameric structure that exhibits substrate-controlled oligomerization.

French, J.B.Yates, P.A.Soysa, D.R.Boitz, J.M.Carter, N.S.Chang, B.Ullman, B.Ealick, S.E.

(2011) J Biol Chem 286: 20930-20941

  • DOI: https://doi.org/10.1074/jbc.M111.228213
  • Primary Citation of Related Structures:  
    3QW3, 3QW4

  • 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.


  • Organizational Affiliation

    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative (Ompdcase-oprtase, putative)
A, B
255Leishmania infantumMutation(s): 0 
Gene Names: LinJ16.0560
EC: 2.4.2.10 (PDB Primary Data), 4.1.1.23 (PDB Primary Data)
UniProt
Find proteins for A4HWV2 (Leishmania infantum)
Explore A4HWV2 
Go to UniProtKB:  A4HWV2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA4HWV2
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.377α = 90
b = 98.165β = 106.54
c = 62.137γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACTdata extraction
ADSCdata collection

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-02-29
    Changes: Database references
  • Version 1.3: 2017-11-08
    Changes: Refinement description
  • Version 1.4: 2024-02-21
    Changes: Data collection, Database references, Derived calculations