2c4f
From Proteopedia
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==Overview== | ==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. | 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. | ||
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Esophageal squamous cell carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606551 606551]], Factor VII deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227500 227500]], Myocardial infarction, decreased susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227500 227500]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:10:30 2007'' |
Revision as of 19:04, 12 November 2007
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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 GLC, FUC, NAG, CA and GIL as ligands. Active as Coagulation factor VIIa, with EC number 3.4.21.21 Structure known Active Site: AC1. 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 Mon Nov 12 21:10:30 2007
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
