2qch

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
[[Image:2qch.jpg|left|200px]]
[[Image:2qch.jpg|left|200px]]
-
{{Structure
+
<!--
-
|PDB= 2qch |SIZE=350|CAPTION= <scene name='initialview01'>2qch</scene>, resolution 1.95&Aring;
+
The line below this paragraph, containing "STRUCTURE_2qch", creates the "Structure Box" on the page.
-
|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>
+
You may change the PDB parameter (which sets the PDB file loaded into the applet)
-
|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>
+
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-
|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>
+
or leave the SCENE parameter empty for the default display.
-
|GENE= UMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+
-->
-
|DOMAIN=
+
{{STRUCTURE_2qch| PDB=2qch | SCENE= }}
-
|RELATEDENTRY=[[2v30|2v30]], [[2jgy|2jgy]]
+
-
|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>
+
-
}}
+
'''Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to 5-iodo-UMP'''
'''Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase bound to 5-iodo-UMP'''
Line 31: Line 28:
[[Category: Rudolph, M.]]
[[Category: Rudolph, M.]]
[[Category: Wittmann, J.]]
[[Category: Wittmann, J.]]
-
[[Category: catalytic proficiency]]
+
[[Category: Catalytic proficiency]]
-
[[Category: decarboxylase]]
+
[[Category: Decarboxylase]]
-
[[Category: lyase]]
+
[[Category: Lyase]]
-
[[Category: ump synthase]]
+
[[Category: Ump synthase]]
-
 
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:43:41 2008''
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:47:38 2008''
+

Revision as of 11:43, 4 May 2008

Image:2qch.jpg

Template:STRUCTURE 2qch

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


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

2QCH 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 14:43:41 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2qch"
Personal tools