2c4f
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The activated factor VII/tissue factor complex (FVIIa/TF) is known to play | + | The activated factor VII/tissue factor complex (FVIIa/TF) is known to play a key role in the formation of blood clots. Inhibition of this complex may lead to new antithrombotic drugs. A fluoropyridine-based series of FVIIa/TF inhibitors was discovered which utilized a diisopropylamino group for binding in the S2 and S3 binding pockets of the active site of the enzyme complex. In this series, an enhancement in binding affinity was observed by substitution at the 5-position of the hydroxybenzoic acid sidechain. An X-ray crystal structure indicates that amides at this position may increase inhibitor binding affinity through interactions with the S1'/S2' pocket. |
==Disease== | ==Disease== | ||
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[[Category: Coagulation factor VIIa]] | [[Category: Coagulation factor VIIa]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Kohrt, J | + | [[Category: Kohrt, J T.]] |
[[Category: Zhang, E.]] | [[Category: Zhang, E.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:44:45 2008'' |
Revision as of 14:44, 21 February 2008
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CRYSTAL STRUCTURE OF FACTOR VII.STF COMPLEXED WITH PD0297121
Contents |
Overview
The activated factor VII/tissue factor complex (FVIIa/TF) is known to play a key role in the formation of blood clots. Inhibition of this complex may lead to new antithrombotic drugs. A fluoropyridine-based series of FVIIa/TF inhibitors was discovered which utilized a diisopropylamino group for binding in the S2 and S3 binding pockets of the active site of the enzyme complex. In this series, an enhancement in binding affinity was observed by substitution at the 5-position of the hydroxybenzoic acid sidechain. An X-ray crystal structure indicates that amides at this position may increase inhibitor binding affinity through interactions with the S1'/S2' pocket.
Disease
Known diseases associated with this structure: Esophageal squamous cell carcinoma OMIM:[606551], Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]
About this Structure
2C4F is a Protein complex structure of sequences from [1] with , , , and as ligands. Active as Coagulation factor VIIa, with EC number 3.4.21.21 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
The discovery of fluoropyridine-based inhibitors of the factor VIIa/TF complex--Part 2., Kohrt JT, Filipski KJ, Cody WL, Cai C, Dudley DA, Van Huis CA, Willardsen JA, Narasimhan LS, Zhang E, Rapundalo ST, Saiya-Cork K, Leadley RJ, Edmunds JJ, Bioorg Med Chem Lett. 2006 Feb 15;16(4):1060-4. Epub 2005 Nov 11. PMID:16289811
Page seeded by OCA on Thu Feb 21 16:44:45 2008
Categories: Coagulation factor VIIa | Protein complex | Kohrt, J T. | Zhang, E. | CA | FUC | GIL | GLC | NAG | Blood coagulation | Egf | Egf-like domain | Gla | Glycoprotein | Hydrolase | Hydroxylation | Lipoprotein | Palmitate | Protease | Receptor enzyme | Serine protease | Transmembrane
