1wss
Human Factor Viia-Tissue Factor in Complex with peprid mimetic inhibitor that has two charge groups in P2 and P4
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OverviewOverview
The crystal structure of human factor VIIa/soluble tissue factor, (FVIIa/sTF) in complex with a highly selective peptide-mimetic FVIIa, inhibitor which shows 1670-fold selectivity against thrombin inhibition, has been solved at 2.6 A resolution. The inhibitor is bound to FVIIa/sTF, at the S1, S2 and S3 sites and at the additional S1 subsite. Two charged, groups, the amidino group in P2 and the carboxylate group in P4, form, ionic interactions with Asp60 and Lys192 of FVIIa, respectively., Structural comparisons between factor VIIa and thrombin show that thrombin, has oppositely charged residues, Lys60F and Glu192, in the S2 site and the, S1 subsites, respectively. These data suggest that the utilization of the, differences of charge distribution in the S2 site and the S1 subsites, between FVIIa and thrombin is critical for achieving high selectivity, against thrombin inhibition. These results will provide valuable, information for the structure-based drug design of specific inhibitors for, FVIIa/TF.
DiseaseDisease
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 StructureAbout this Structure
1WSS is a Protein complex structure of sequences from Homo sapiens with BGC, FUC, CA and 3CB as ligands. Active as Coagulation factor VIIa, with EC number 3.4.21.21 Full crystallographic information is available from OCA.
ReferenceReference
Structure of human factor VIIa/tissue factor in complex with a peptide-mimetic inhibitor: high selectivity against thrombin by introducing two charged groups in P2 and P4., Kadono S, Sakamoto A, Kikuchi Y, Oh-Eda M, Yabuta N, Koga T, Hattori K, Shiraishi T, Haramura M, Kodama H, Ono Y, Esaki T, Sato H, Watanabe Y, Itoh S, Ohta M, Kozono T, Acta Crystallograph Sect F Struct Biol Cryst Commun. 2005 Feb 1;61(Pt, 2):169-73. Epub 2005 Jan 20. PMID:16510984
Page seeded by OCA on Mon Nov 12 19:54:26 2007