2fpt
From Proteopedia
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|PDB= 2fpt |SIZE=350|CAPTION= <scene name='initialview01'>2fpt</scene>, resolution 2.400Å | |PDB= 2fpt |SIZE=350|CAPTION= <scene name='initialview01'>2fpt</scene>, resolution 2.400Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ILB:2-({[3,5-DIFLUORO-3'-(TRIFLUOROMETHOXY)BIPHENYL-4-YL]AMINO}CARBONYL)CYCLOPENT-1-ENE-1-CARBOXYLIC+ACID'>ILB</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= DHODH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= DHODH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2bxv|2BXV]], [[2fpv|2FPV]], [[2fpy|2FPY]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fpt OCA], [http://www.ebi.ac.uk/pdbsum/2fpt PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fpt RCSB]</span> | ||
}} | }} | ||
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[[Category: Tasler, S.]] | [[Category: Tasler, S.]] | ||
[[Category: Walloschek, M.]] | [[Category: Walloschek, M.]] | ||
| - | [[Category: ACT]] | ||
| - | [[Category: FMN]] | ||
| - | [[Category: ILB]] | ||
| - | [[Category: ORO]] | ||
| - | [[Category: SO4]] | ||
[[Category: protein inhibitor complex]] | [[Category: protein inhibitor complex]] | ||
| - | ''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 03:06:07 2008'' |
Revision as of 00:06, 31 March 2008
| |||||||
| , resolution 2.400Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Gene: | DHODH (Homo sapiens) | ||||||
| Activity: | Dihydroorotate oxidase, with EC number 1.3.3.1 | ||||||
| Related: | 2BXV, 2FPV, 2FPY
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
2FPT is a Single protein structure of sequence from Homo sapiens. 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 Mon Mar 31 03:06:07 2008
