1uum

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[[Image:1uum.jpg|left|200px]]<br /><applet load="1uum" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1uum.jpg|left|200px]]
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caption="1uum, resolution 2.3&Aring;" />
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'''RAT DIHYDROOROTATE DEHYDROGENASE (DHOD)IN COMPLEX WITH ATOVAQUONE'''<br />
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{{Structure
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|PDB= 1uum |SIZE=350|CAPTION= <scene name='initialview01'>1uum</scene>, resolution 2.3&Aring;
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|SITE= <scene name='pdbsite=AC1:Bog+Binding+Site+For+Chain+B'>AC1</scene>
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|LIGAND= <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene> and <scene name='pdbligand=AFI:2-[4-(4-CHLOROPHENYL)CYCLOHEXYLIDENE]-3,4-DIHYDROXY-1(2H)-NAPHTHALENONE'>AFI</scene>
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|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]
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|GENE=
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}}
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'''RAT DIHYDROOROTATE DEHYDROGENASE (DHOD)IN COMPLEX WITH ATOVAQUONE'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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].
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1UUM is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_rattus Rattus rattus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UUM OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15044733 15044733]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15044733 15044733]
[[Category: Dihydroorotate dehydrogenase]]
[[Category: Dihydroorotate dehydrogenase]]
[[Category: Rattus rattus]]
[[Category: Rattus rattus]]
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[[Category: transit peptide]]
[[Category: transit peptide]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:28:36 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:37:00 2008''

Revision as of 12:37, 20 March 2008

Image:1uum.jpg


PDB ID 1uum

Drag the structure with the mouse to rotate
, resolution 2.3Å
Sites:
Ligands: , , and
Activity: Dihydroorotate dehydrogenase, with EC number 1.3.99.11
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

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