1uum
From Proteopedia
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| - | [[Image:1uum.jpg|left|200px]]<br /><applet load="1uum" size=" | + | [[Image:1uum.jpg|left|200px]]<br /><applet load="1uum" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1uum, resolution 2.3Å" /> | caption="1uum, resolution 2.3Å" /> | ||
'''RAT DIHYDROOROTATE DEHYDROGENASE (DHOD)IN COMPLEX WITH ATOVAQUONE'''<br /> | '''RAT DIHYDROOROTATE DEHYDROGENASE (DHOD)IN COMPLEX WITH ATOVAQUONE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1UUM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_rattus Rattus rattus] with BOG, FMN, ORO and AFI as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:Bog Binding Site For Chain B'>AC1</scene>. Full crystallographic information is available from [http:// | + | 1UUM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_rattus Rattus rattus] with <scene name='pdbligand=BOG:'>BOG</scene>, <scene name='pdbligand=FMN:'>FMN</scene>, <scene name='pdbligand=ORO:'>ORO</scene> and <scene name='pdbligand=AFI:'>AFI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:Bog+Binding+Site+For+Chain+B'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UUM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transit peptide]] | [[Category: transit peptide]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:08:10 2008'' |
Revision as of 08:08, 3 February 2008
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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 with , , and as ligands. Active as Dihydroorotate dehydrogenase, with EC number 1.3.99.11 Known structural/functional Site: . 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
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Categories: Dihydroorotate dehydrogenase | Rattus rattus | Single protein | Antal, T. | Hansen, M. | Johansson, E. | Larsen, S. | Loffler, M. | Nours, J.Le. | Ullrich, A. | AFI | BOG | FMN | ORO | Atovaquone | Brequinar | Fad | Flavoprotein | Nucleotide metabolism | Oxidoreductase | Pyrimidine biosynthesis | Transit peptide
