Liu W, Takayanagi R, Ito T, Oba K, Nawata H
The Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
FEBS Lett. 1997 Dec 22;420(1):103-6. doi: 10.1016/s0014-5793(97)01497-x.
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 (Ki=20.6 microM) and [Ala31]big ET-1(18-34) to be a noncompetitive inhibitor (Ki=35.6 microM). 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.
