1DVA

Crystal Structure of the Complex Between the Peptide Exosite Inhibitor E-76 and Coagulation Factor VIIA

Summary for 1DVA

• Entry DOI: 10.2210/pdb1dva/pdb
• Related: 1CVW 1DAN 1FAK 1QFK
• Related PRD ID: PRD_000369 PRD_900004
• Descriptor: DES-GLA FACTOR VIIA (HEAVY CHAIN), beta-L-fucopyranose, DES-GLA FACTOR VIIA (LIGHT CHAIN), ... (11 entities in total)
• Functional Keywords: protein-peptide complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 85049.09

Authors

Eigenbrot, C.,Ultsch, M.H. (deposition date: 2000-01-20, release date: 2000-05-12, Last modification date: 2024-10-30)

Primary citation

Dennis, M.S.,Eigenbrot, C.,Skelton, N.J.,Ultsch, M.H.,Santell, L.,Dwyer, M.A.,O'Connell, M.P.,Lazarus, R.A.
Peptide exosite inhibitors of factor VIIa as anticoagulants.
Nature, 404:465-470, 2000

PubMed Abstract: 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.

PubMed: 10761907
DOI: 10.1038/35006574

Experimental method

X-RAY DIFFRACTION (3 Å)