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2qcc
From Proteopedia
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|PDB= 2qcc |SIZE=350|CAPTION= <scene name='initialview01'>2qcc</scene>, resolution 1.85Å | |PDB= 2qcc |SIZE=350|CAPTION= <scene name='initialview01'>2qcc</scene>, resolution 1.85Å | ||
|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Residue+A+481'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Residue+B+481'>AC2</scene>, <scene name='pdbsite=AC3:Gol+Binding+Site+For+Residue+A+482'>AC3</scene> and <scene name='pdbsite=AC4:Gol+Binding+Site+For+Residue+B+482'>AC4</scene> | |SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Residue+A+481'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Residue+B+481'>AC2</scene>, <scene name='pdbsite=AC3:Gol+Binding+Site+For+Residue+A+482'>AC3</scene> and <scene name='pdbsite=AC4:Gol+Binding+Site+For+Residue+B+482'>AC4</scene> | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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= UMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= UMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2v30|2v30]], [[2jgy|2jgy]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qcc OCA], [http://www.ebi.ac.uk/pdbsum/2qcc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qcc RCSB]</span> | ||
}} | }} | ||
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[[Category: Rudolph, M.]] | [[Category: Rudolph, M.]] | ||
[[Category: Wittmann, J.]] | [[Category: Wittmann, J.]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: SO4]] | ||
[[Category: catalytic proficiency]] | [[Category: catalytic proficiency]] | ||
[[Category: decarboxylase]] | [[Category: decarboxylase]] | ||
| Line 36: | Line 37: | ||
[[Category: ump synthase]] | [[Category: ump synthase]] | ||
| - | ''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 04:47:36 2008'' |
Revision as of 01:47, 31 March 2008
| |||||||
| , resolution 1.85Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , and | ||||||
| Ligands: | , | ||||||
| Gene: | UMPS (Homo sapiens) | ||||||
| Activity: | Orotidine-5'-phosphate decarboxylase, with EC number 4.1.1.23 | ||||||
| Related: | 2v30, 2jgy
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase, apo form
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
2QCC 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 Mon Mar 31 04:47:36 2008
