2bxv
From Proteopedia
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| - | [[Image:2bxv.gif|left|200px]]<br /><applet load="2bxv" size=" | + | [[Image:2bxv.gif|left|200px]]<br /><applet load="2bxv" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2bxv, resolution 2.15Å" /> | caption="2bxv, resolution 2.15Å" /> | ||
'''DUAL BINDING MODE OF A NOVEL SERIES OF DHODH INHIBITORS'''<br /> | '''DUAL BINDING MODE OF A NOVEL SERIES OF DHODH INHIBITORS'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2BXV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4, ACT, FMN, ORO and 3FT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dihydroorotate_oxidase Dihydroorotate oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.3.1 1.3.3.1] Known structural/functional Site: <scene name='pdbsite=AC1:3ft Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http:// | + | 2BXV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=FMN:'>FMN</scene>, <scene name='pdbligand=ORO:'>ORO</scene> and <scene name='pdbligand=3FT:'>3FT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dihydroorotate_oxidase Dihydroorotate oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.3.1 1.3.3.1] Known structural/functional Site: <scene name='pdbsite=AC1:3ft+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BXV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: virtual high-throughput screening]] | [[Category: virtual high-throughput screening]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:29:06 2008'' |
Revision as of 08:29, 3 February 2008
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DUAL BINDING MODE OF A NOVEL SERIES OF DHODH INHIBITORS
Overview
Human dihydroorotate dehydrogenase (DHODH) represents an important target, for the treatment of hyperproliferative and inflammatory diseases. In the, cell DHODH catalyzes the rate-limiting step of the de novo pyrimidine, biosynthesis. DHODH inhibition results in beneficial immunosuppressant and, antiproliferative effects in diseases such as rheumatoid arthritis. Here, we present high-resolution X-ray structures of human DHODH in complex with, a novel class of low molecular weight compounds that inhibit the enzyme in, the nanomolar range. Some compounds showed an interesting dual binding, mode within the same cocrystal strongly depending on the nature of, chemical substitution. Measured in vitro activity data correlated with the, prevailing mode of binding and explained the observed structure-activity, relationship. Additionally, the X-ray data confirmed the competitive, nature of the inhibitors toward the putative ubiquinone binding site and, will guide structure-based design and synthesis of molecules with higher, activity.
About this Structure
2BXV is a Single protein structure of sequence from Homo sapiens with , , , and as ligands. Active as Dihydroorotate oxidase, with EC number 1.3.3.1 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Dual binding mode of a novel series of DHODH inhibitors., Baumgartner R, Walloschek M, Kralik M, Gotschlich A, Tasler S, Mies J, Leban J, J Med Chem. 2006 Feb 23;49(4):1239-47. PMID:16480261
Page seeded by OCA on Sun Feb 3 10:29:06 2008
Categories: Dihydroorotate oxidase | Homo sapiens | Single protein | Baumgartner, R. | Gotschlich, A. | Karlik, M. | Leban, J. | Mies, J. | Tasler, S. | Walloschek, M. | 3FT | ACT | FMN | ORO | SO4 | Dihydroorotate dehydrogenase inhibitor | Dual binding mode | Rheumatoid arthritis oxidoreductase | Virtual high-throughput screening
