Proteolytic processing of porcine big endothelin-1 catalyzed by cathepsin D.
Cathepsin D, a candidate for endothelin-converting enzyme (ECE), was allowed to act on porcine big endothelin-1 (big ET-1, 1-39). The proteinase primarily cleaved the Asp18-Ile19 and Trp21-Val22 bonds of big ET-1(1-39), with a optimum pH of 3.5. The mature ET-1(1-21), generated by the cleavage between Trp21 and Val22, was subsequently degraded by removal of most of the C-terminal tripeptide (Ile19-Ile20-Trp21). Therefore, cathepsin D is by no means a specific ECE, although the proteinase does cleave the Trp21-Val22 bond of big ET-1(1-39) to produce mature ET-1(1-21). The possibility that cathepsin D can act as an endothelin-degrading enzyme in vivo warrants consideration.
Takaoka
M
M
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Hukumori
Y
Y
Shiragami
K
K
Ikegawa
R
R
Matsumura
Y
Y
Morimoto
S
S
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000378:metabolism*; D006868:Hydrolysis; D008666:Metalloendopeptidases; D008969:Molecular Sequence Data; D013552:Swine
D016232:Endothelins; D016282:Aspartic Acid Endopeptidases; D002402:Cathepsin D; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes