1dva
From Proteopedia
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CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN THE PEPTIDE EXOSITE INHIBITOR E-76 AND COAGULATION FACTOR VIIA
Contents |
Overview
Potent anticoagulants have been derived by targeting the tissue factor-factor VIIa complex with naive peptide libraries displayed on M13 phage. The peptides specifically block the activation of factor X with a median inhibitory concentration of 1 nM and selectively inhibit tissue-factor-dependent clotting. The peptides do not bind to the active site of factor VIIa; rather, they work by binding to an exosite on the factor VIIa protease domain, and non-competitively inhibit activation of factor X and amidolytic activity. One such peptide (E-76) has a well defined structure in solution determined by NMR spectroscopy that is similar to the X-ray crystal structure when complexed with factor VIIa. These structural and functional studies indicate an allosteric 'switch' mechanism of inhibition involving an activation loop of factor VIIa and represent a new framework for developing inhibitors of serine proteases.
Disease
Known diseases associated with this structure: Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]
About this Structure
1DVA is a Single protein structure of sequence from Homo sapiens with , , , , , and as ligands. Active as Coagulation factor VIIa, with EC number 3.4.21.21 Full crystallographic information is available from OCA.
Reference
Peptide exosite inhibitors of factor VIIa as anticoagulants., Dennis MS, Eigenbrot C, Skelton NJ, Ultsch MH, Santell L, Dwyer MA, O'Connell MP, Lazarus RA, Nature. 2000 Mar 30;404(6777):465-70. PMID:10761907
Page seeded by OCA on Thu Feb 21 12:20:50 2008
Categories: Coagulation factor VIIa | Homo sapiens | Single protein | Eigenbrot, C. | Ultsch, M H. | ACE | CA | CAC | CH2 | FUC | FUL | GLC | Protein-peptide complex
