The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor.
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.
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D W
DW
Pharma Division, F. Hoffmann-La Roche, Basle, Switzerland.
D'Arcy
A
A
Chène
C
C
Winkler
F K
FK
Guha
A
A
Konigsberg
W H
WH
Nemerson
Y
Y
Kirchhofer
D
D
D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D005164:Factor IX / Q000378:metabolism; D015942:Factor VIIa / Q000737:chemistry* / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013381:Subtilisins; D013925:Thromboplastin / Q000737:chemistry* / Q000378:metabolism
D011994:Recombinant Proteins; D005164:Factor IX; D005170:Factor X; D013925:Thromboplastin; D013381:Subtilisins; D015942:Factor VIIa