2qch

From Proteopedia

(Difference between revisions)

Revision as of 00:19, 12 September 2015

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

Structural highlights

2qch is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	2v30, 2jgy
Gene:	UMPS (HUMAN)
Activity:	Orotidine-5'-phosphate decarboxylase, with EC number 4.1.1.23
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[UMPS_HUMAN] Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM: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.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Suchi M, Mizuno H, Kawai Y, Tsuboi T, Sumi S, Okajima K, Hodgson ME, Ogawa H, Wada Y. Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. Am J Hum Genet. 1997 Mar;60(3):525-39. PMID:9042911
↑ Wittmann JG, Heinrich D, Gasow K, Frey A, Diederichsen U, Rudolph MG. Structures of the human orotidine-5'-monophosphate decarboxylase support a covalent mechanism and provide a framework for drug design. Structure. 2008 Jan;16(1):82-92. PMID:18184586 doi:http://dx.doi.org/10.1016/j.str.2007.10.020

1 Structural highlights
2 Disease
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 2: / Line 2: @@
 <StructureSection load='2qch' size='340' side='right' caption='[[2qch]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2qch]] is a 2 chain structure with 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QCH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2qch]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QCH FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2v30|2v30]], [[2jgy|2jgy]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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.rcsb.org/pdb/explore.do?structureId=2qch RCSB], [http://www.ebi.ac.uk/pdbsum/2qch PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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://pdbe.org/2qch PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qch RCSB], [http://www.ebi.ac.uk/pdbsum/2qch PDBsum]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/PYR5_HUMAN PYR5_HUMAN]] Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM:[http://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>
+[[http://www.uniprot.org/uniprot/UMPS_HUMAN UMPS_HUMAN]] Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM:[http://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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2qch" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 36: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Orotidine-5'-phosphate decarboxylase]]
 [[Category: Rudolph, M]]

2qch

From Proteopedia

Revision as of 00:19, 12 September 2015

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

Structural highlights

Disease

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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