1dva
From Proteopedia
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|PDB= 1dva |SIZE=350|CAPTION= <scene name='initialview01'>1dva</scene>, resolution 3.00Å | |PDB= 1dva |SIZE=350|CAPTION= <scene name='initialview01'>1dva</scene>, resolution 3.00Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=CH2:METHYLENE+GROUP'>CH2</scene>, <scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1dan|1DAN]], [[1cvw|1CVW]], [[1qfk|1QFK]], [[1fak|1FAK]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dva FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dva OCA], [http://www.ebi.ac.uk/pdbsum/1dva PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dva RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227500 227500]], Myocardial infarction, decreased susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227500 227500]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Eigenbrot, C.]] | [[Category: Eigenbrot, C.]] | ||
[[Category: Ultsch, M H.]] | [[Category: Ultsch, M H.]] | ||
| - | [[Category: ACE]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: CAC]] | ||
| - | [[Category: CH2]] | ||
| - | [[Category: FUC]] | ||
| - | [[Category: FUL]] | ||
| - | [[Category: GLC]] | ||
[[Category: protein-peptide complex]] | [[Category: protein-peptide complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:49:23 2008'' |
Revision as of 16:49, 30 March 2008
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| , resolution 3.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , , , , , , | ||||||
| Activity: | Coagulation factor VIIa, with EC number 3.4.21.21 | ||||||
| Related: | 1DAN, 1CVW, 1QFK, 1FAK
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN THE PEPTIDE EXOSITE INHIBITOR E-76 AND COAGULATION FACTOR VIIA
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
