2qce

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[[Image:2qce.jpg|left|200px]]
[[Image:2qce.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 2qce |SIZE=350|CAPTION= <scene name='initialview01'>2qce</scene>, resolution 1.43&Aring;
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The line below this paragraph, containing "STRUCTURE_2qce", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Residue+A+481'>AC1</scene>, <scene name='pdbsite=AC2:Gol+Binding+Site+For+Residue+A+484'>AC2</scene> and <scene name='pdbsite=AC3:Gol+Binding+Site+For+Residue+A+485'>AC3</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=S:SULFUR+ATOM'>S</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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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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or leave the SCENE parameter empty for the default display.
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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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-->
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|DOMAIN=
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{{STRUCTURE_2qce| PDB=2qce | SCENE= }}
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|RELATEDENTRY=[[2qcc|2qcc]], [[2qcd|2qcd]], [[2v30|2v30]], [[2jgy|2jgy]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qce OCA], [http://www.ebi.ac.uk/pdbsum/2qce PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qce RCSB]</span>
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}}
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'''Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to sulfate, glycerol, and chloride'''
'''Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to sulfate, glycerol, and chloride'''
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[[Category: Rudolph, M.]]
[[Category: Rudolph, M.]]
[[Category: Wittmann, J.]]
[[Category: Wittmann, J.]]
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[[Category: catalytic proficiency]]
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[[Category: Catalytic proficiency]]
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[[Category: decarboxylase]]
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[[Category: Decarboxylase]]
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[[Category: lyase]]
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[[Category: Lyase]]
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[[Category: ump synthase]]
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[[Category: Ump synthase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:43:28 2008''
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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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Revision as of 11:43, 4 May 2008

Image:2qce.jpg

Template:STRUCTURE 2qce

Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to sulfate, glycerol, and chloride


Contents

Overview

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.

Disease

Known disease associated with this structure: Oroticaciduria OMIM:[258900]

About this Structure

2QCE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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:18184586 Page seeded by OCA on Sun May 4 14:43:28 2008

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