2e6y
From Proteopedia
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| - | [[Image:2e6y.gif|left|200px]] | + | [[Image:2e6y.gif|left|200px]] |
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| - | '''Covalent complex of orotidine 5'-monophosphate decarboxylase (ODCase) with 6-Iodo-UMP''' | + | {{Structure |
| + | |PDB= 2e6y |SIZE=350|CAPTION= <scene name='initialview01'>2e6y</scene>, resolution 1.60Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=U5P:URIDINE-5'-MONOPHOSPHATE'>U5P</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.23 4.1.1.23] | ||
| + | |GENE= pyrF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=145262 Methanothermobacter thermautotrophicus]) | ||
| + | }} | ||
| + | |||
| + | '''Covalent complex of orotidine 5'-monophosphate decarboxylase (ODCase) with 6-Iodo-UMP''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2E6Y is a [ | + | 2E6Y is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus Methanothermobacter thermautotrophicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E6Y OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17290979 17290979] |
[[Category: Methanothermobacter thermautotrophicus]] | [[Category: Methanothermobacter thermautotrophicus]] | ||
[[Category: Orotidine-5'-phosphate decarboxylase]] | [[Category: Orotidine-5'-phosphate decarboxylase]] | ||
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[[Category: tim-barrel]] | [[Category: tim-barrel]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:36:06 2008'' |
Revision as of 14:36, 20 March 2008
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| , resolution 1.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | pyrF (Methanothermobacter thermautotrophicus) | ||||||
| Activity: | Orotidine-5'-phosphate decarboxylase, with EC number 4.1.1.23 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Covalent complex of orotidine 5'-monophosphate decarboxylase (ODCase) with 6-Iodo-UMP
Overview
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.
About this Structure
2E6Y is a Single protein structure of sequence from Methanothermobacter thermautotrophicus. Full crystallographic information is available from OCA.
Reference
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
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