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FVIIa derivatives obtained by autolytic and controlled cathepsin G mediated cleavage
Author(s) -
Nicolaisen Else Marie,
Thim Lars,
Jacobsen Jes Kristian,
Nielsen Per Franklin,
Mollerup Inger,
Jørgensen Tony,
Hedner Ulla
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81285-8
Subject(s) - autolysis (biology) , zymogen , cleavage (geology) , chemistry , trypsin , chymotrypsin , biochemistry , cathepsin , serine , enzyme , biology , paleontology , fracture (geology)
The heavy chain of coagulation factor VII contains a serine esterase entity. A partial cleavage in the heavy chain occurs during purification and activation of the single‐chain zymogen, presumably as a result of autolysis. Neutrophil cathepsin G initially generates a Gla‐domainless FVIIa without coagulant activity. However, on extended exposure cleavage also occurs in the heavy chain, resulting in a complete loss of enzyme activity. Four cleavage sites on the heavy chain, two susceptible to trypsin‐like autolysis and two susceptible to chymotrypsin‐like cathepsin G‐mediated catalysis have been identified. The hydrolysis of peptide bonds in the heavy chain might contribute to regulation of the coagulation process in vivo.