Importance of the C-terminal region of big endothelin-1 for specific conversion by phosphoramidon-sensitive endothelin converting enzyme.
Based on our previous findings that phosphoramidon-sensitive endothelin (ET) converting enzyme (ECE) converts human big ET-1 but does not big ET-3, we investigated structural requirement for substrate peptide. We prepared shorter peptides of big ET-1 and measured hydrolysis of the Trp-Val bond of these peptides. Relative hydrolysis ratios of big ET-1(1-38), (1-37), (16-37), (1-31) and (17-26) were 1, 1.15, 3.71, 0.01 and 0, respectively. In addition, big ET-2 and big ET-3 were not significantly converted by ECE. These results suggest that the carboxyl-terminal sequence at residues 32-37 of big ET-1 is important for conversion, whereas the amino-terminal disulfide loop structure appears to interfere with access of ECE to big ET-1.
Okada
K
K
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Takada
J
J
Arai
Y
Y
Matsuyama
K
K
Yano
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002417:Cattle; D003600:Cytosol / Q000201:enzymology; D019332:Endothelin-1; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology; D006020:Glycopeptides / Q000494:pharmacology*; D006801:Humans; D008666:Metalloendopeptidases; D008861:Microsomes / Q000201:enzymology; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D010455:Peptides; D011498:Protein Precursors; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon