2qce: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2qce.jpg|left|200px]] | [[Image:2qce.jpg|left|200px]] | ||
'''Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to sulfate, glycerol, and chloride''' | {{Structure | ||
|PDB= 2qce |SIZE=350|CAPTION= <scene name='initialview01'>2qce</scene>, resolution 1.43Å | |||
|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> | |||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=S:SULFUR+ATOM'>S</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</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] | |||
|GENE= UMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to sulfate, glycerol, and chloride''' | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
2QCE is a [ | 2QCE 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=2QCE OCA]. | ||
==Reference== | ==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:[http:// | 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] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Orotidine-5'-phosphate decarboxylase]] | [[Category: Orotidine-5'-phosphate decarboxylase]] | ||
| Line 28: | Line 37: | ||
[[Category: ump synthase]] | [[Category: ump synthase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:24:16 2008'' | ||
Revision as of 16:24, 20 March 2008
| |||||||||||||
| 2qce, resolution 1.43Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sites: | AC1, AC2 and AC3 | ||||||||||||
| Ligands: | SO4, CL, S and GOL | ||||||||||||
| Gene: | UMPS (Homo sapiens) | ||||||||||||
| Activity: | Orotidine-5'-phosphate decarboxylase, with EC number 4.1.1.23 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to sulfate, glycerol, and chloride
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 Thu Mar 20 18:24:16 2008
