FVIIa derivatives obtained by autolytic and controlled cathepsin G mediated cleavage.
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.
Nicolaisen
E M
EM
Novo Nordisk, Novo Alle, Bagsvaerd, Denmark.
Thim
L
L
Jacobsen
J K
JK
Nielsen
P F
PF
Mollerup
I
I
Jørgensen
T
T
Hedner
U
U
D000595:Amino Acid Sequence; D001329:Autolysis; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel; D015942:Factor VIIa / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D017421:Sequence Analysis; D012697:Serine Endopeptidases
D011994:Recombinant Proteins; D002403:Cathepsins; D012697:Serine Endopeptidases; D056649:Cathepsin G; D015942:Factor VIIa