View source for 1uuo


==Rat dihydroorotate dehydrogenase (DHOD)in complex with brequinar==
<StructureSection load='1uuo' size='340' side='right'caption='[[1uuo]], [[Resolution|resolution]] 2.44&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1uuo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_rattus Rattus rattus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UUO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.44&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BRF:6-FLUORO-2-(2-FLUORO-1,1-BIPHENYL-4-YL)-3-METHYLQUINOLINE-4-CARBOXYLIC+ACID'>BRF</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uuo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uuo OCA], [https://pdbe.org/1uuo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uuo RCSB], [https://www.ebi.ac.uk/pdbsum/1uuo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uuo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PYRD_RAT PYRD_RAT] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.[HAMAP-Rule:MF_00225]
== 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/uu/1uuo_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=1uuo ConSurf].
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== Publication Abstract from PubMed ==
The flavin enzyme dihydroorotate dehydrogenase (DHOD; EC 1.3.99.11) catalyzes the oxidation of dihydroorotate to orotate, the fourth step in the de novo pyrimidine biosynthesis of UMP. The enzyme is a promising target for drug design in different biological and clinical applications for cancer and arthritis. The first crystal structure of the class 2 dihydroorotate dehydrogenase from rat has been determined in complex with its two inhibitors brequinar and atovaquone. These inhibitors have shown promising results as anti-proliferative, immunosuppressive, and antiparasitic agents. A unique feature of the class 2 DHODs is their N-terminal extension, which folds into a separate domain comprising two alpha-helices. This domain serves as the binding site for the two inhibitors and the respiratory quinones acting as the second substrate for the class 2 DHODs. The orientation of the first N-terminal helix is very different in the two complexes of rat DHOD (DHODR). Binding of atovaquone causes a 12 A movement of the first residue in the first alpha-helix. Based on the information from the two structures of DHODR, a model for binding of the quinone and the residues important for the interactions could be defined. His 56 and Arg 136, which are fully conserved in all class 2 DHODs, seem to play a key role in the interaction with the electron acceptor. The differences between the membrane-bound rat DHOD and membrane-associated class 2 DHODs exemplified by the Escherichia coli DHOD has been investigated by GRID computations of the hydrophobic probes predicted to interact with the membrane.

Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain.,Hansen M, Le Nours J, Johansson E, Antal T, Ullrich A, Loffler M, Larsen S Protein Sci. 2004 Apr;13(4):1031-42. PMID:15044733<ref>PMID:15044733</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1uuo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dihydroorotate dehydrogenase 3D structures|Dihydroorotate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus rattus]]
[[Category: Antal T]]
[[Category: Hansen M]]
[[Category: Johansson E]]
[[Category: Larsen S]]
[[Category: Le Nours J]]
[[Category: Loffler M]]
[[Category: Ullrich A]]