Importance of the C-terminal region of big endothelin-1 for specific conversion by phosphoramidon-sensitive endothelin converting enzyme |
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Authors: | K Okada J Takada Y Arai K Matsuyama M Yano |
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Institution: | Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan. |
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Abstract: | 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. |
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