1WTG

Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-biphenylalanine-Gln-p-aminobenzamidine

Summary for 1WTG

• Entry DOI: 10.2210/pdb1wtg/pdb
• Related: 1DAN 1WQV 1WSS
• Descriptor: Coagulation factor VII, Tissue factor, beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: serine protease, hydrolase-blood clotting complex, hydrolase/blood clotting
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 71585.45

Authors

Kadono, S.,Sakamoto, S.,Kikuchi, Y.,Oh-Eda, M.,Yabuta, N.,Kitazawa, K.,Yoshihashi, T.,Suzuki, T.,Koga, T.,Hattori, K.,Shiraishi, T.,Kodama, M.,Haramura, H.,Ono, Y.,Esaki, T.,Sato, H.,Watanabe, Y.,Itoh, S.,Ohta, M.,Kozono, T. (deposition date: 2004-11-23, release date: 2005-11-23, Last modification date: 2023-11-15)

Primary citation

Kadono, S.,Sakamoto, A.,Kikuchi, Y.,Oh-Eda, M.,Yabuta, N.,Yoshihashi, K.,Kitazawa, T.,Suzuki, T.,Koga, T.,Hattori, K.,Shiraishi, T.,Haramura, M.,Kodama, H.,Ono, Y.,Esaki, T.,Sato, H.,Watanabe, Y.,Itoh, S.,Ohta, M.,Kozono, T.
Novel interactions of large P3 moiety and small P4 moiety in the binding of the peptide mimetic factor VIIa inhibitor
Biochem.Biophys.Res.Commun., 326:859-865, 2005

PubMed Abstract: Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen as a promising target for developing new anticoagulant drugs. A novel peptide mimetic factor VIIa inhibitor, ethylsulfonamide-d-biphenylalanine-Gln-p-aminobenzamidine, shows 100-fold selectivity against thrombin in spite of its large P3 moiety, unlike previously reported FVIIa/TF selective inhibitors. X-ray crystal structure analysis reveals that the large P3 moiety, d-biphenylalanine, and the small P4 moiety, ethylsulfonamide, make novel interactions with the 170-loop and Lys192 of FVIIa/TF, respectively, accompanying ligand-induced conformational changes of the 170-loop, Gln217, and Lys192. Structural comparisons of FVIIa with thrombin and amino acid sequence comparisons among coagulation serine proteases suggest that these interactions play an important role in achieving selective inhibition for FVIIa/TF.

PubMed: 15607748
DOI: 10.1016/j.bbrc.2004.11.108

Experimental method

X-RAY DIFFRACTION (2.2 Å)