1uum
From Proteopedia
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|PDB= 1uum |SIZE=350|CAPTION= <scene name='initialview01'>1uum</scene>, resolution 2.3Å | |PDB= 1uum |SIZE=350|CAPTION= <scene name='initialview01'>1uum</scene>, resolution 2.3Å | ||
|SITE= <scene name='pdbsite=AC1:Bog+Binding+Site+For+Chain+B'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Bog+Binding+Site+For+Chain+B'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=AFI:2-[4-(4-CHLOROPHENYL)CYCLOHEXYLIDENE]-3,4-DIHYDROXY-1(2H)-NAPHTHALENONE'>AFI</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Dihydroorotate_dehydrogenase Dihydroorotate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.99.11 1.3.99.11] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydroorotate_dehydrogenase Dihydroorotate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.99.11 1.3.99.11] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uum OCA], [http://www.ebi.ac.uk/pdbsum/1uum PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1uum RCSB]</span> | ||
}} | }} | ||
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[[Category: Nours, J Le.]] | [[Category: Nours, J Le.]] | ||
[[Category: Ullrich, A.]] | [[Category: Ullrich, A.]] | ||
| - | [[Category: AFI]] | ||
| - | [[Category: BOG]] | ||
| - | [[Category: FMN]] | ||
| - | [[Category: ORO]] | ||
[[Category: atovaquone]] | [[Category: atovaquone]] | ||
[[Category: brequinar]] | [[Category: brequinar]] | ||
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[[Category: transit peptide]] | [[Category: transit peptide]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:15:30 2008'' |
Revision as of 21:15, 30 March 2008
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| , resolution 2.3Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , , | ||||||
| Activity: | Dihydroorotate dehydrogenase, with EC number 1.3.99.11 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
RAT DIHYDROOROTATE DEHYDROGENASE (DHOD)IN COMPLEX WITH ATOVAQUONE
Overview
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.
About this Structure
1UUM is a Single protein structure of sequence from Rattus rattus. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Mar 31 00:15:30 2008
Categories: Dihydroorotate dehydrogenase | Rattus rattus | Single protein | Antal, T. | Hansen, M. | Johansson, E. | Larsen, S. | Loffler, M. | Nours, J Le. | Ullrich, A. | Atovaquone | Brequinar | Fad | Flavoprotein | Nucleotide metabolism | Oxidoreductase | Pyrimidine biosynthesis | Transit peptide
