2qch

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[[Image:2qch.jpg|left|200px]]
 
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{{Structure
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==Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to 5-iodo-UMP==
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|PDB= 2qch |SIZE=350|CAPTION= <scene name='initialview01'>2qch</scene>, resolution 1.95&Aring;
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<StructureSection load='2qch' size='340' side='right'caption='[[2qch]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:Iod+Binding+Site+For+Residue+A+5'>AC1</scene>, <scene name='pdbsite=AC2:Iod+Binding+Site+For+Residue+B+6'>AC2</scene>, <scene name='pdbsite=AC3:5iu+Binding+Site+For+Residue+A+1'>AC3</scene>, <scene name='pdbsite=AC4:Ump+Binding+Site+For+Residue+A+2'>AC4</scene>, <scene name='pdbsite=AC5:5iu+Binding+Site+For+Residue+B+3'>AC5</scene> and <scene name='pdbsite=AC6:Ump+Binding+Site+For+Residue+B+4'>AC6</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=5IU:5-IODO-2&#39;-DEOXYURIDINE-5&#39;-MONOPHOSPHATE'>5IU</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=UMP:2&#39;-DEOXYURIDINE+5&#39;-MONOPHOSPHATE'>UMP</scene>
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<table><tr><td colspan='2'>[[2qch]] 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=2QCH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QCH FirstGlance]. <br>
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|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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
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|GENE= UMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5IU:5-IODO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>5IU</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qch OCA], [https://pdbe.org/2qch PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qch RCSB], [https://www.ebi.ac.uk/pdbsum/2qch PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qch ProSAT]</span></td></tr>
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|RELATEDENTRY=[[2v30|2v30]], [[2jgy|2jgy]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qch OCA], [http://www.ebi.ac.uk/pdbsum/2qch PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qch RCSB]</span>
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== Disease ==
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}}
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[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>
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== Function ==
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[https://www.uniprot.org/uniprot/UMPS_HUMAN UMPS_HUMAN]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qc/2qch_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/main_output.php?pdb_ID=2qch ConSurf].
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<div style="clear:both"></div>
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'''Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to 5-iodo-UMP'''
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==See Also==
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*[[Uridine 5'-monophosphate synthase 3D structures|Uridine 5'-monophosphate synthase 3D structures]]
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== References ==
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==Overview==
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<references/>
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UMP synthase (UMPS) catalyzes the last two steps of de novo pyrimidine nucleotide synthesis and is a potential cancer drug target. The C-terminal domain of UMPS is orotidine-5'-monophosphate decarboxylase (OMPD), a cofactor-less yet extremely efficient enzyme. Studies of OMPDs from micro-organisms led to the proposal of several noncovalent decarboxylation mechanisms via high-energy intermediates. We describe nine crystal structures of human OMPD in complex with substrate, product, and nucleotide inhibitors. Unexpectedly, simple compounds can replace the natural nucleotides and induce a closed conformation of OMPD, defining a tripartite catalytic site. The structures outline the requirements drugs must meet to maximize therapeutic effects and minimize cross-species activity. Chemical mimicry by iodide identified a CO(2) product binding site. Plasticity of catalytic residues and a covalent OMPD-UMP complex prompt a reevaluation of the prevailing decarboxylation mechanism in favor of covalent intermediates. This mechanism can also explain the observed catalytic promiscuity of OMPD.
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: Oroticaciduria OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=258900 258900]]
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==About this Structure==
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2QCH is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QCH OCA].
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==Reference==
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Structures of the human orotidine-5'-monophosphate decarboxylase support a covalent mechanism and provide a framework for drug design., Wittmann JG, Heinrich D, Gasow K, Frey A, Diederichsen U, Rudolph MG, Structure. 2008 Jan;16(1):82-92. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18184586 18184586]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Orotidine-5'-phosphate decarboxylase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Rudolph M]]
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[[Category: Rudolph, M.]]
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[[Category: Wittmann J]]
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[[Category: Wittmann, J.]]
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[[Category: catalytic proficiency]]
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[[Category: decarboxylase]]
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[[Category: lyase]]
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[[Category: ump synthase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:47:38 2008''
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Current revision

Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to 5-iodo-UMP

PDB ID 2qch

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