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[Phe 21 ]big endothelin‐1(18–34) and [Ala 31 ]big endothelin‐1(18–34) inhibit the human endothelin‐converting enzyme‐1 (ECE‐1) expressed in CHO‐K1 cells in a different fashion
Author(s) -
Liu Wei,
Takayanagi Ryoichi,
Ito Takeshi,
Oba Koichi,
Nawata Hajime
Publication year - 1997
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/s0014-5793(97)01497-x
Subject(s) - enzyme , chemistry , endothelin 1 , endothelin receptor , membrane , stereochemistry , biochemistry , receptor
Endothelin‐converting enzyme‐1 (ECE‐1) is one of the most important enzymes to convert big endothelin‐1 (big ET‐1) to ET‐1. To identify the inhibitors of ECE‐1, we examined the effects of variously substituted analogues of big ET‐1 on ECE‐1 activity using solubilized membranes prepared from human ECE‐1‐expressed CHO‐K1 cells. Among the big ET‐1 analogues tested, [Phe 21 ]big ET‐1(18–34) and [Ala 31 ]big ET‐1(18–34) exhibited a significant inhibition of ECE‐1. A kinetic analysis revealed [Phe 21 ]big ET‐1(18–34) to be a competitive inhibitor ( K i =20.6 μM) and [Ala 31 ]big ET‐1(18–34) to be a non‐competitive inhibitor ( K i =35.6 μM). These results not only support the concept that ECE‐1 recognizes big ET‐1 both at the P1 position and at the C‐terminal region but also revealed that these two regions are recognized by this enzyme in a different manner.