Abstract
Blood coagulation is initiated when tissue factor binds to coagulation factor VIIa to give an enzymatically active complex which then activates factors IX and X, leading to thrombin generation and clot formation. We have determined the crystal structure at 2.0-A degrees resolution of active-site-inhibited factor VIIa complexed with the cleaved extracellular domain of tissue factor. In the complex, factor VIIa adopts an extended conformation. This structure provides a basis for understanding many molecular aspects of the initiation of coagulation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Catalysis
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Crystallography, X-Ray
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Factor IX / metabolism
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Factor VIIa / chemistry*
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Factor VIIa / metabolism
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Factor X / metabolism
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Humans
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Models, Molecular
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Molecular Sequence Data
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Protein Binding
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Protein Conformation
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Recombinant Proteins / chemistry
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Structure-Activity Relationship
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Substrate Specificity
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Subtilisins
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Thromboplastin / chemistry*
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Thromboplastin / metabolism
Substances
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Recombinant Proteins
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Factor IX
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Factor X
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Thromboplastin
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Subtilisins
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Factor VIIa