1dva | pdb_00001dva
CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN THE PEPTIDE EXOSITE INHIBITOR E-76 AND COAGULATION FACTOR VIIA
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| 1dva, resolution 3.00Å | |||||||||||||
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| Ligands: | ACE, BGC, CA, CAC, CH2, DPN, FUC, FUL, GAL, GLC | ||||||||||||
| Activity: | Coagulation factor VIIa, with EC number 3.4.21.21 | ||||||||||||
| Related: | 1DAN, 1CVW, 1QFK, 1FAK
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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.
About this Structure
1DVA is a Single protein structure of sequence from Homo sapiens. 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 Sun Mar 30 19:49:23 2008
