2e6y | pdb_00002e6y

Covalent complex of orotidine 5'-monophosphate decarboxylase (ODCase) with 6-Iodo-UMP

spinqualitylabelsall models 2e6y, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2e6y is a 2 chain structure with sequence from "methanobacterium_thermoautotrophicus"_(sic)_zeikus_and_wolfe_1972 "methanobacterium thermoautotrophicus" (sic) zeikus and wolfe 1972. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, U5P Related: 1dv7, 1dvj, 1kly, 1klz, 1km0, 1km1, 1km2, 1km3, 1km4, 1km5, 1km6, 1lol, 1loq, 1lor, 1los, 1lp6, 1x1z Gene: pyrF ("Methanobacterium thermoautotrophicus" (sic) Zeikus and Wolfe 1972) Activity: Orotidine-5'-phosphate decarboxylase, with EC number 4.1.1.23 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [PYRF_METTH] Catalyzes the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP).[HAMAP-Rule:MF_01200_A] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Orotidine 5'-monophosphate decarboxylase (ODCase) has evolved to catalyze the decarboxylation of orotidine 5'-monophosphate without any covalent intermediates. Active site residues in ODCase are involved in an extensive hydrogen-bonding network. We discovered that 6-iodouridine 5'-monophosphate (6-iodo-UMP) irreversibly inhibits the catalytic activities of ODCases from Methanobacterium thermoautotrophicum and Plasmodium falciparum. Mass spectral analysis of the enzyme-inhibitor complex confirms covalent attachment of the inhibitor to ODCase accompanied by the loss of two protons and the iodo moiety. The X-ray crystal structure (1.6 A resolution) of the complex of the inhibitor and ODCase clearly shows the covalent bond formation with the active site Lys-72 [corrected] residue. 6-Iodo-UMP inhibits ODCase in a time- and concentration-dependent fashion. 6-Iodouridine, the nucleoside form of 6-iodo-UMP, exhibited potent antiplasmodial activity, with IC50s of 4.4 +/- 1.3 microM and 6.2 +/- 0.7 microM against P. falciparum ItG and 3D7 isolates, respectively. 6-Iodouridine 5'-monophosphate is a novel covalent inhibitor of ODCase, and its nucleoside analogue paves the way to a new class of inhibitors against malaria. A potent, covalent inhibitor of orotidine 5'-monophosphate decarboxylase with antimalarial activity.,Bello AM, Poduch E, Fujihashi M, Amani M, Li Y, Crandall I, Hui R, Lee PI, Kain KC, Pai EF, Kotra LP J Med Chem. 2007 Mar 8;50(5):915-21. Epub 2007 Feb 10. PMID:17290979 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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