1WUN

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

Summary for 1WUN

• Entry DOI: 10.2210/pdb1wun/pdb
• Related: 1DAN 1WQV 1WSS 1WTG
• 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: 71548.39

Authors

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. (deposition date: 2004-12-08, release date: 2005-12-08, 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.
Structure-based design of P3 moieties in the peptide mimetic factor VIIa inhibitor
Biochem.Biophys.Res.Commun., 327:589-596, 2005

PubMed Abstract: Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen as a promising target for developing new anticoagulant drugs. Structure-based designs of the P3 moiety in the peptide mimetic factor VIIa inhibitor successfully lead to novel inhibitors with selectivity for FVIIa/TF and extrinsic coagulation the same as or even higher than those of previously reported peptide mimetic factor VIIa inhibitors. X-ray crystal structure analysis reveals that one of the novel inhibitors shows improved selectivity by forming interactions between the inhibitor and FVIIa as expected. Another of the novel inhibitors achieves improved selectivity through an unexpected hydrogen bond with Gln217, with a unique bent conformation in FVIIa/TF accompanied by conformational changes of the inhibitor and the protein.

PubMed: 15629154
DOI: 10.1016/j.bbrc.2004.12.042

Experimental method

X-RAY DIFFRACTION (2.4 Å)