1Z6J

Crystal Structure of a ternary complex of Factor VIIa/Tissue Factor/Pyrazinone Inhibitor

Summary for 1Z6J

• Entry DOI: 10.2210/pdb1z6j/pdb
• Descriptor: Coagulation factor VII, Tissue factor, CALCIUM ION, ... (7 entities in total)
• Functional Keywords: blood coagulation, serine protease, thrombosis, gla, pyrazinone, benzamidine, tissue factor, cofactor, enzyme inhibitor complex, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 69040.68

Authors

Schweitzer, B.A.,Neumann, W.L.,Rahman, H.K.,Kusturin, C.L.,Sample, K.R.,Poda, G.I.,Kurumbail, R.G.,Stevens, A.M.,Stegeman, R.A.,Stallings, W.C. (deposition date: 2005-03-22, release date: 2005-05-03, Last modification date: 2019-07-24)

Primary citation

Schweitzer, B.A.,Neumann, W.L.,Rahman, H.K.,Kusturin, C.L.,Sample, K.R.,Poda, G.I.,Kurumbail, R.G.,Stevens, A.M.,Stegeman, R.A.,Stallings, W.C.,South, M.S.
Structure-based design and synthesis of pyrazinones containing novel P1 'side pocket' moieties as inhibitors of TF/VIIa.
Bioorg.Med.Chem.Lett., 15:3006-3011, 2005

PubMed Abstract: We describe the structure-based design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors contain substituents meta to the P(1) amidine designed to explore additional interactions with the VIIa residues in the so-called 'S(1) side pocket'. A crystal structure of the designed inhibitors demonstrates the ability of the P(1) side pocket moiety to engage Lys192 and main chain of Gly216 via hydrogen bond interactions, thus, providing additional possibility for chemical modification to improve selectivity and/or physical properties of inhibitors.

PubMed: 15913999
DOI: 10.1016/j.bmcl.2005.04.037

Experimental method

X-RAY DIFFRACTION (2 Å)