2ZCG

Structure and inhibition of orotidine 5'-phosphate decarboxylase from plasmodium falciparum

Summary for 2ZCG

• Entry DOI: 10.2210/pdb2zcg/pdb
• Descriptor: Orotidine 5'-phosphate decarboxylase (2 entities in total)
• Functional Keywords: tim barrel, decarboxylase, lyase, pyrimidine biosynthesis
• Biological source: Plasmodium falciparum (malaria parasite P. falciparum)
• Total number of polymer chains: 2
• Total formula weight: 75732.49

Authors

Langley, D.B.,Guss, J.M.,Shojaei, M.,Christopherson, R.I. (deposition date: 2007-11-08, release date: 2008-03-11, Last modification date: 2023-11-01)

Primary citation

Langley, D.B.,Shojaei, M.,Chan, C.,Lok, H.C.,Mackay, J.P.,Traut, T.W.,Guss, J.M.,Christopherson, R.I.
Structure and Inhibition of Orotidine 5'-Monophosphate Decarboxylase from Plasmodium falciparum
Biochemistry, 47:3842-3854, 2008

PubMed Abstract: Orotidine 5'-monophosphate (OMP) decarboxylase from Plasmodium falciparum (PfODCase, EC 4.1.1.23) has been overexpressed, purified, subjected to kinetic and biochemical analysis, and crystallized. The native enzyme is a homodimer with a subunit molecular mass of 38 kDa. The saturation curve for OMP as a substrate conformed to Michaelis-Menten kinetics with K m = 350 +/- 60 nM and V max = 2.70 +/- 0.10 micromol/min/mg protein. Inhibition patterns for nucleoside 5'-monophosphate analogues were linear competitive with respect to OMP with a decreasing potency of inhibition of PfODCase in the order: pyrazofurin 5'-monophosphate ( K i = 3.6 +/- 0.7 nM) > xanthosine 5'-monophosphate (XMP, K i = 4.4 +/- 0.7 nM) > 6-azauridine 5'-monophosphate (AzaUMP, K i = 12 +/- 3 nM) > allopurinol-3-riboside 5'-monophosphate ( K i = 240 +/- 20 nM). XMP is an approximately 150-fold more potent inhibitor of PfODCase compared with the human enzyme. The structure of PfODCase was solved in the absence of ligand and displays a classic TIM-barrel fold characteristic of the enzyme. Both the phosphate-binding loop and the betaalpha5-loop have conformational flexibility, which may be associated with substrate capture and product release along the reaction pathway.

PubMed: 18303855
DOI: 10.1021/bi702390k

Experimental method

X-RAY DIFFRACTION (2.223 Å)