[Phe21]big endothelin‐1(18–34) and [Ala31]big endothelin‐1(18–34) inhibit the human endothelin‐converting enzyme‐1 (ECE‐1) expressed in CHO‐K1 cells in a different fashion

FEBS Letters

Oba, Koichi¹  Nawata, Hajime¹  Liu, Wei¹  Ito, Takeshi¹  Takayanagi, Ryoichi¹ 

[1] The Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-82, Japan

关键词: Endothelin;    Endothelin-converting enzyme;    Big endothelin;    Big endothelin analogue;   

DOI  :  10.1016/S0014-5793(97)01497-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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, [Phe²¹]big ET-1(18–34) and [Ala³¹]big ET-1(18–34) exhibited a significant inhibition of ECE-1. A kinetic analysis revealed [Phe²¹]big ET-1(18–34) to be a competitive inhibitor (K _i=20.6 μM) and [Ala³¹]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.

【 授权许可】

Unknown