1wss: Difference between revisions

[[Image:1wss.gif|left|200px]]<br /><applet load="1wss" size="350" color="white" frame="true" align="right" spinBox="true"  

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.

1WSS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=BGC:'>BGC</scene>, <scene name='pdbligand=FUC:'>FUC</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=3CB:'>3CB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_VIIa Coagulation factor VIIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.21 3.4.21.21] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WSS OCA].  

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 Crystallogr Sect F Struct Biol Cryst Commun. 2005 Feb 1;61(Pt, 2):169-73. Epub 2005 Jan 20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16510984 16510984]

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