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| | <StructureSection load='1uuo' size='340' side='right'caption='[[1uuo]], [[Resolution|resolution]] 2.44Å' scene=''> | | <StructureSection load='1uuo' size='340' side='right'caption='[[1uuo]], [[Resolution|resolution]] 2.44Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1uuo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Black_rat Black rat]. 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 [http://proteopedia.org/fgij/fg.htm?mol=1UUO FirstGlance]. <br> | + | <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='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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.44Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1uum|1uum]]</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydroorotate_dehydrogenase_(quinone) Dihydroorotate dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.5.2 1.3.5.2] </span></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> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1uuo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uuo OCA], [http://pdbe.org/1uuo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uuo RCSB], [http://www.ebi.ac.uk/pdbsum/1uuo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1uuo ProSAT]</span></td></tr> | + | |
| | </table> | | </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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Black rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Antal, T]] | + | [[Category: Rattus rattus]] |
| - | [[Category: Hansen, M]] | + | [[Category: Antal T]] |
| - | [[Category: Johansson, E]] | + | [[Category: Hansen M]] |
| - | [[Category: Larsen, S]] | + | [[Category: Johansson E]] |
| - | [[Category: Loffler, M]] | + | [[Category: Larsen S]] |
| - | [[Category: Nours, J Le]] | + | [[Category: Le Nours J]] |
| - | [[Category: Ullrich, A]] | + | [[Category: Loffler M]] |
| - | [[Category: Atovaquone]]
| + | [[Category: Ullrich A]] |
| - | [[Category: Brequinar]]
| + | |
| - | [[Category: Dihydroorotate dehydrogenase]]
| + | |
| - | [[Category: Nucleotide metabolism]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
1uuo is a 1 chain structure with sequence from Rattus rattus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.44Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
PYRD_RAT Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.[HAMAP-Rule:MF_00225]
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
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hansen M, Le Nours J, Johansson E, Antal T, Ullrich A, Loffler M, Larsen S. Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci. 2004 Apr;13(4):1031-42. PMID:15044733 doi:10.1110/ps.03533004
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