2zcg
From Proteopedia
Structure and inhibition of orotidine 5'-phosphate decarboxylase from plasmodium falciparum
Structural highlights
FunctionEvolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedOrotidine 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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