2qcc: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(11 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2qcc.jpg|left|200px]]


<!--
==Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase, apo form==
The line below this paragraph, containing "STRUCTURE_2qcc", creates the "Structure Box" on the page.
<StructureSection load='2qcc' size='340' side='right'caption='[[2qcc]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2qcc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QCC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QCC FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
-->
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_2qcc| PDB=2qcc |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qcc OCA], [https://pdbe.org/2qcc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qcc RCSB], [https://www.ebi.ac.uk/pdbsum/2qcc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qcc ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/UMPS_HUMAN UMPS_HUMAN] Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM:[https://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>
== Function ==
[https://www.uniprot.org/uniprot/UMPS_HUMAN UMPS_HUMAN]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qc/2qcc_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2qcc ConSurf].
<div style="clear:both"></div>


'''Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase, apo form'''
==See Also==
 
*[[Uridine 5'-monophosphate synthase 3D structures|Uridine 5'-monophosphate synthase 3D structures]]
 
== References ==
==Overview==
<references/>
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.
__TOC__
 
</StructureSection>
==Disease==
Known disease associated with this structure: Oroticaciduria OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=258900 258900]]
 
==About this Structure==
2QCC 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=2QCC 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:[http://www.ncbi.nlm.nih.gov/pubmed/18184586 18184586]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Orotidine-5'-phosphate decarboxylase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Rudolph M]]
[[Category: Rudolph, M.]]
[[Category: Wittmann J]]
[[Category: Wittmann, J.]]
[[Category: Catalytic proficiency]]
[[Category: Decarboxylase]]
[[Category: Lyase]]
[[Category: Tim barrel]]
[[Category: Ump synthase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 14:43:09 2008''

Latest revision as of 12:15, 21 February 2024

Crystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase, apo formCrystal structure of the orotidine-5'-monophosphate decarboxylase domain of human UMP synthase, apo form

Structural highlights

2qcc is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.85Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Function

UMPS_HUMAN

Evolutionary Conservation

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

See Also

References

  1. ↑ 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

2qcc, resolution 1.85Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=2qcc&oldid=4062736"