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| {{STRUCTURE_2e6y| PDB=2e6y | SCENE= }} | | {{STRUCTURE_2e6y| PDB=2e6y | SCENE= }} |
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| '''Covalent complex of orotidine 5'-monophosphate decarboxylase (ODCase) with 6-Iodo-UMP'''
| | ===Covalent complex of orotidine 5'-monophosphate decarboxylase (ODCase) with 6-Iodo-UMP=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17290979}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17290979 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17290979}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Pai, E F.]] | | [[Category: Pai, E F.]] |
| [[Category: Tim-barrel]] | | [[Category: Tim-barrel]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 02:02:42 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:33:59 2008'' |
