1wtg
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| , resolution 2.20Å | |||||||
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| Ligands: | , , , , | ||||||
| Activity: | Coagulation factor VIIa, with EC number 3.4.21.21 | ||||||
| Related: | 1WSS, 1WQV, 1DAN
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-biphenylalanine-Gln-p-aminobenzamidine
OverviewOverview
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.
About this StructureAbout this Structure
1WTG is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Novel interactions of large P3 moiety and small P4 moiety in the binding of the peptide mimetic factor VIIa inhibitor., 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, Biochem Biophys Res Commun. 2005 Jan 28;326(4):859-65. PMID:15607748
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