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'''Structure and inhibition of orotidine 5'-phosphate decarboxylase from plasmodium falciparum''' | '''Structure and inhibition of orotidine 5'-phosphate decarboxylase from plasmodium falciparum''' | ||
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[[Category: Langley, D B.]] | [[Category: Langley, D B.]] | ||
[[Category: Shojaei, M.]] | [[Category: Shojaei, M.]] | ||
[[Category: | [[Category: Decarboxylase]] | ||
[[Category: | [[Category: Lyase]] | ||
[[Category: | [[Category: Pyrimidine biosynthesis]] | ||
[[Category: | [[Category: Tim barrel]] | ||
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Revision as of 17:08, 4 May 2008
Structure and inhibition of orotidine 5'-phosphate decarboxylase from plasmodium falciparum
Overview
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.
About this Structure
2ZCG is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.
Reference
Structure and Inhibition of Orotidine 5'-Monophosphate Decarboxylase from Plasmodium falciparum., Langley DB, Shojaei M, Chan C, Lok HC, Mackay JP, Traut TW, Guss JM, Christopherson RI, Biochemistry. 2008 Feb 28;. PMID:18303855 Page seeded by OCA on Sun May 4 20:08:40 2008
