2AEI

Crystal structure of a ternary complex of factor VIIa/tissue factor and 2-[[6-[3-(aminoiminomethyl)phenoxy]-3,5-difluro-4-[(1-methyl-3-phenylpropyl)amino]-2-pyridinyl]oxy]-benzoic acid

Summary for 2AEI

• Entry DOI: 10.2210/pdb2aei/pdb
• Related: 1DAN 1W0Y 1W2K 1YGC 1Z6J
• Descriptor: Coagulation factor VII, Tissue factor, CALCIUM ION, ... (7 entities in total)
• Functional Keywords: blood coagulation, serine protease, thrombosis, gla, pyridine, benzamidine, tissue factor, cofactor, enzyme inhibitor complex, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P08709 P08709; Membrane; Single-pass type I membrane protein: P13726
• Total number of polymer chains: 3
• Total formula weight: 70400.93

Authors

Adler, M.,Whitlow, M. (deposition date: 2005-07-22, release date: 2006-08-01, Last modification date: 2023-11-15)

Primary citation

Kohrt, J.T.,Filipski, K.J.,Cody, W.L.,Cai, C.,Dudley, D.A.,Van Huis, C.A.,Willardsen, J.A.,Rapundalo, S.T.,Saiya-Cork, K.,Leadley, R.J.,Narasimhan, L.,Zhang, E.,Whitlow, M.,Adler, M.,McLean, K.,Chou, Y.L.,McKnight, C.,Arnaiz, D.O.,Shaw, K.J.,Light, D.R.,Edmunds, J.J.
The discovery of fluoropyridine-based inhibitors of the Factor VIIa/TF complex.
Bioorg.Med.Chem.Lett., 15:4752-4756, 2005

PubMed Abstract: The activated Factor VII/tissue factor complex (FVIIa/TF) plays a key role in the formation of blood clots. Inhibition of this complex may lead to new antithrombotic drugs. An X-ray crystal structure of a fluoropyridine-based FVIIa/TF inhibitor bound in the active site of the enzyme complex suggested that incorporation of substitution at the 5-position of the hydroxybenzoic acid side chain could lead to the formation of more potent inhibitors through interactions with the S1'/S2' pocket.

PubMed: 16125385
DOI: 10.1016/j.bmcl.2005.07.059

Experimental method

X-RAY DIFFRACTION (2.52 Å)