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| | ==Crystal structure of human orotidine-5'-monophosphate decarboxylase complexed with pyrazofurin monophosphate== | | ==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=''> | + | <StructureSection load='3mi2' size='340' side='right'caption='[[3mi2]], [[Resolution|resolution]] 1.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mi2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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> | + | <table><tr><td colspan='2'>[[3mi2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <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='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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mi2 OCA], [https://pdbe.org/3mi2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mi2 RCSB], [https://www.ebi.ac.uk/pdbsum/3mi2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mi2 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gi|13960142, OK/SW-cl.21, UMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <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>
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| - | <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://pdbe.org/3mi2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mi2 RCSB], [http://www.ebi.ac.uk/pdbsum/3mi2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mi2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == 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> | + | [https://www.uniprot.org/uniprot/UMPS_HUMAN UMPS_HUMAN] Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM:[https://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 == |
| | + | [https://www.uniprot.org/uniprot/UMPS_HUMAN UMPS_HUMAN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Phosphoribosyltransferase|Phosphoribosyltransferase]] | + | *[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]] |
| - | *[[Uridine 5'-monophosphate synthase|Uridine 5'-monophosphate synthase]] | + | *[[Uridine 5'-monophosphate synthase 3D structures|Uridine 5'-monophosphate synthase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Orotidine-5'-phosphate decarboxylase]] | + | [[Category: Large Structures]] |
| - | [[Category: Kotra, L P]] | + | [[Category: Kotra LP]] |
| - | [[Category: Liu, Y]] | + | [[Category: Liu Y]] |
| - | [[Category: Pai, E F]] | + | [[Category: Pai EF]] |
| - | [[Category: To, T]] | + | [[Category: To T]] |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Orotidine 5'-monophosphate decarboxylase]]
| + | |
| - | [[Category: Pyrazofurin monophosphate]]
| + | |
| - | [[Category: Ump synthase]]
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| Structural highlights
Disease
UMPS_HUMAN Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM: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.[1]
Function
UMPS_HUMAN
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
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Suchi M, Mizuno H, Kawai Y, Tsuboi T, Sumi S, Okajima K, Hodgson ME, Ogawa H, Wada Y. Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. Am J Hum Genet. 1997 Mar;60(3):525-39. PMID:9042911
- ↑ Meza-Avina ME, Wei L, Liu Y, Poduch E, Bello AM, Mishra RK, Pai EF, Kotra LP. Structural determinants for the inhibitory ligands of orotidine-5'-monophosphate decarboxylase. Bioorg Med Chem. 2010 Jun 1;18(11):4032-41. Epub 2010 Apr 9. PMID:20452222 doi:10.1016/j.bmc.2010.04.017
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