3mi2
From Proteopedia
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| - | + | ==Crystal structure of human orotidine-5'-monophosphate decarboxylase complexed with pyrazofurin monophosphate== | |
| - | + | <StructureSection load='3mi2' size='340' side='right' caption='[[3mi2]], [[Resolution|resolution]] 1.20Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[3mi2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MI2 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PFU:(1S)-1,4-ANHYDRO-1-(5-CARBAMOYL-4-HYDROXY-1H-PYRAZOL-3-YL)-5-O-PHOSPHONO-D-RIBITOL'>PFU</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2eaw|2eaw]], [[2p1f|2p1f]], [[3bgg|3bgg]], [[3bgj|3bgj]], [[3g3d|3g3d]], [[3bko|3bko]], [[3bvj|3bvj]], [[3g3m|3g3m]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3mi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mi2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3mi2 RCSB], [http://www.ebi.ac.uk/pdbsum/3mi2 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/UMPS_HUMAN UMPS_HUMAN]] Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM:[http://omim.org/entry/258900 258900]]. A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. A minority of cases have additional features, particularly congenital malformations and immune deficiencies.<ref>PMID:9042911</ref> | ||
| + | == Function == | ||
| - | == | + | == Evolutionary Conservation == |
| - | [[ | + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mi/3mi2_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In recent years, orotidine-5'-monophosphate decarboxylase (ODCase) has gained renewed attention as a drug target. As a part of continuing efforts to design novel inhibitors of ODCase, we undertook a comprehensive study of potent, structurally diverse ligands of ODCase and analyzed their structural interactions in the active site of ODCase. These ligands comprise of pyrazole or pyrimidine nucleotides including the mononucleotide derivatives of pyrazofurin, barbiturate ribonucleoside, and 5-cyanouridine, as well as, in a computational approach, 1,4-dihydropyridine-based non-nucleoside inhibitors such as nifedipine and nimodipine. All these ligands bind in the active site of ODCase exhibiting distinct interactions paving the way to design novel inhibitors against this interesting enzyme. We propose an empirical model for the ligand structure for rational modifications in new drug design and potentially new lead structures. | ||
| - | + | Structural determinants for the inhibitory ligands of orotidine-5'-monophosphate decarboxylase.,Meza-Avina ME, Wei L, Liu Y, Poduch E, Bello AM, Mishra RK, Pai EF, Kotra LP Bioorg Med Chem. 2010 Jun 1;18(11):4032-41. Epub 2010 Apr 9. PMID:20452222<ref>PMID:20452222</ref> | |
| - | + | ||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
==See Also== | ==See Also== | ||
*[[Phosphoribosyltransferase|Phosphoribosyltransferase]] | *[[Phosphoribosyltransferase|Phosphoribosyltransferase]] | ||
*[[Uridine 5'-monophosphate synthase|Uridine 5'-monophosphate synthase]] | *[[Uridine 5'-monophosphate synthase|Uridine 5'-monophosphate synthase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
[[Category: Orotidine-5'-phosphate decarboxylase]] | [[Category: Orotidine-5'-phosphate decarboxylase]] | ||
| - | [[Category: Kotra, L P | + | [[Category: Kotra, L P]] |
| - | [[Category: Liu, Y | + | [[Category: Liu, Y]] |
| - | [[Category: Pai, E F | + | [[Category: Pai, E F]] |
| - | [[Category: To, T | + | [[Category: To, T]] |
[[Category: Lyase]] | [[Category: Lyase]] | ||
[[Category: Orotidine 5'-monophosphate decarboxylase]] | [[Category: Orotidine 5'-monophosphate decarboxylase]] | ||
[[Category: Pyrazofurin monophosphate]] | [[Category: Pyrazofurin monophosphate]] | ||
[[Category: Ump synthase]] | [[Category: Ump synthase]] | ||
Revision as of 07:26, 12 November 2014
Crystal structure of human orotidine-5'-monophosphate decarboxylase complexed with pyrazofurin monophosphate
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