2e6y
From Proteopedia
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|PDB= 2e6y |SIZE=350|CAPTION= <scene name='initialview01'>2e6y</scene>, resolution 1.60Å | |PDB= 2e6y |SIZE=350|CAPTION= <scene name='initialview01'>2e6y</scene>, resolution 1.60Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=U5P:URIDINE-5'-MONOPHOSPHATE'>U5P</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= pyrF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=145262 Methanothermobacter thermautotrophicus]) | |GENE= pyrF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=145262 Methanothermobacter thermautotrophicus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1dv7|1dv7]], [[1dvj|1dvj]], [[1kly|1kly]], [[1klz|1klz]], [[1km0|1km0]], [[1km1|1km1]], [[1km2|1km2]], [[1km3|1km3]], [[1km4|1km4]], [[1km5|1km5]], [[1km6|1km6]], [[1lol|1lol]], [[1loq|1loq]], [[1lor|1lor]], [[1los|1los]], [[1lp6|1lp6]], [[1x1z|1x1z]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2e6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e6y OCA], [http://www.ebi.ac.uk/pdbsum/2e6y PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2e6y RCSB]</span> | ||
}} | }} | ||
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[[Category: Kotra, L P.]] | [[Category: Kotra, L P.]] | ||
[[Category: Pai, E F.]] | [[Category: Pai, E F.]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: U5P]] | ||
[[Category: tim-barrel]] | [[Category: tim-barrel]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:44:36 2008'' |
Revision as of 23:44, 30 March 2008
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| , resolution 1.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | pyrF (Methanothermobacter thermautotrophicus) | ||||||
| Activity: | Orotidine-5'-phosphate decarboxylase, with EC number 4.1.1.23 | ||||||
| Related: | 1dv7, 1dvj, 1kly, 1klz, 1km0, 1km1, 1km2, 1km3, 1km4, 1km5, 1km6, 1lol, 1loq, 1lor, 1los, 1lp6, 1x1z
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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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