1wtg

From Proteopedia

---

Revision as of 17:48, 12 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 1wtg, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Esophageal squamous cell carcinoma OMIM:[606551], Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]

About this Structure

1WTG is a Protein complex structure of sequences from Homo sapiens with BGC, FUC, CA and 3BP as ligands. Active as Coagulation factor VIIa, with EC number 3.4.21.21 Full crystallographic information is available from OCA.

Reference

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

Page seeded by OCA on Mon Nov 12 19:54:51 2007