1fak: Difference between revisions
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'''HUMAN TISSUE FACTOR COMPLEXED WITH COAGULATION FACTOR VIIA INHIBITED WITH A BPTI-MUTANT''' | {{Structure | ||
|PDB= 1fak |SIZE=350|CAPTION= <scene name='initialview01'>1fak</scene>, resolution 2.1Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene> and <scene name='pdbligand=CA:CALCIUM ION'>CA</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] | |||
|GENE= | |||
}} | |||
'''HUMAN TISSUE FACTOR COMPLEXED WITH COAGULATION FACTOR VIIA INHIBITED WITH A BPTI-MUTANT''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1FAK is a [ | 1FAK is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FAK OCA]. | ||
==Reference== | ==Reference== | ||
Structure of extracellular tissue factor complexed with factor VIIa inhibited with a BPTI mutant., Zhang E, St Charles R, Tulinsky A, J Mol Biol. 1999 Feb 5;285(5):2089-104. PMID:[http:// | Structure of extracellular tissue factor complexed with factor VIIa inhibited with a BPTI mutant., Zhang E, St Charles R, Tulinsky A, J Mol Biol. 1999 Feb 5;285(5):2089-104. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9925787 9925787] | ||
[[Category: Coagulation factor VIIa]] | [[Category: Coagulation factor VIIa]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:06:36 2008'' | ||
Revision as of 12:06, 20 March 2008
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| , resolution 2.1Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | Coagulation factor VIIa, with EC number 3.4.21.21 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN TISSUE FACTOR COMPLEXED WITH COAGULATION FACTOR VIIA INHIBITED WITH A BPTI-MUTANT
OverviewOverview
The event that initiates the extrinsic pathway of blood coagulation is the association of coagulation factor VIIa (VIIa) with its cell-bound receptor, tissue factor (TF), exposed to blood circulation following tissue injury and/or vascular damage. The natural inhibitor of the TF.VIIa complex is the first Kunitz domain of tissue factor pathway inhibitor (TFPI-K1). The structure of TF. VIIa reversibly inhibited with a potent (Ki=0.4 nM) bovine pancreatic trypsin inhibitor (BPTI) mutant (5L15), a homolog of TFPI-K1, has been determined at 2.1 A resolution. When bound to TF, the four domain VIIa molecule assumes an extended conformation with its light chain wrapping around the framework of the two domain TF cofactor. The 5L15 inhibitor associates with the active site of VIIa similar to trypsin-bound BPTI, but makes several unique interactions near the perimeter of the site that are not observed in the latter. Most of the interactions are polar and involve mutated positions of 5L15. Of the eight rationally engineered mutations distinguishing 5L15 from BPTI, seven are involved in productive interactions stabilizing the enzyme-inhibitor association with four contributing contacts unique to the VIIa.5L15 complex. Two additional unique interactions are due to distinguishing residues in the VIIa sequence: a salt bridge between Arg20 of 5L15 and Asp60 of an insertion loop of VIIa, and a hydrogen bond between Tyr34O of the inhibitor and Lys192NZ of the enzyme. These interactions were used further to model binding of TFPI-K1 to VIIa and TFPI-K2 to factor Xa, the principal activation product of TF.VIIa. The structure of the ternary protein complex identifies the determinants important for binding within and near the active site of VIIa, and provides cogent information for addressing the manner in which substrates of VIIa are bound and hydrolyzed in blood coagulation. It should also provide guidance in structure-aided drug design for the discovery of potent and selective small molecule VIIa inhibitors.
DiseaseDisease
Known diseases associated with this structure: Esophageal squamous cell carcinoma OMIM:[606551], Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]
About this StructureAbout this Structure
1FAK is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structure of extracellular tissue factor complexed with factor VIIa inhibited with a BPTI mutant., Zhang E, St Charles R, Tulinsky A, J Mol Biol. 1999 Feb 5;285(5):2089-104. PMID:9925787
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