4JZD

Structure of factor VIIA in complex with the inhibitor 2-{2-[(4-carbamimidoylphenyl)carbamoyl]-6-methoxypyridin-3-yl}-5-{[(2S)-1-hydroxy-3,3-dimethylbutan-2-yl]carbamoyl}benzoic acid

Summary for 4JZD

• Entry DOI: 10.2210/pdb4jzd/pdb
• Related: 4JZE 4JZF
• Descriptor: Factor VIIa (Heavy Chain), Factor VIIa (Light Chain), 2-{2-[(4-carbamimidoylphenyl)carbamoyl]-6-methoxypyridin-3-yl}-5-{[(2S)-1-hydroxy-3,3-dimethylbutan-2-yl]carbamoyl}benzoic acid, ... (7 entities in total)
• Functional Keywords: glycoprotein, serine protease, plasma, blood coagulation factor, protein inhibitor complex, calcium binding, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P08709 P08709
• Total number of polymer chains: 2
• Total formula weight: 35909.78

Authors

Jacobson, B.L.,Anumula, R. (deposition date: 2013-04-02, release date: 2013-08-21, Last modification date: 2024-10-30)

Primary citation

Bolton, S.A.,Sutton, J.C.,Anumula, R.,Bisacchi, G.S.,Jacobson, B.,Slusarchyk, W.A.,Treuner, U.D.,Wu, S.C.,Zhao, G.,Pi, Z.,Sheriff, S.,Smirk, R.A.,Bisaha, S.,Cheney, D.L.,Wei, A.,Schumacher, W.A.,Hartl, K.S.,Liu, E.,Zahler, R.,Seiler, S.M.
Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold.
Bioorg.Med.Chem.Lett., 23:5239-5243, 2013

PubMed Abstract: In this Letter, we describe the synthesis of several nonamidine analogs of biaryl acid factor VIIa inhibitor 1 containing weakly basic or nonbasic P1 groups. 2-Aminoisoquinoline was found to be an excellent surrogate for the benzamidine group (compound 2) wherein potent inhibition of factor VIIa is maintained relative to most other related serine proteases. In an unanticipated result, the m-benzamide P1 (compounds 21a and 21b) proved to be a viable benzamidine replacement, albeit with a 20-40 fold loss in potency against factor VIIa.

PubMed: 23927973
DOI: 10.1016/j.bmcl.2013.06.028

Experimental method

X-RAY DIFFRACTION (2.2 Å)