Characterization of the Active Site of Angiotensin Converting Enzyme

Abstract

Angiotensin converting enzyme is part of the well-known renin-angiotensin system, which consists of a sequence of proteolytic cleavage steps that lead to the generation of the biologically active peptide, angiotensin II (1,2). The initiation of the system involves the secretion of renin, an acid protease, from the kidneys into the blood, where it cleaves the α₂-globulin, angiotensinogen, to yield the decapeptide angiotensin I. Subsequently, angiotensin converting enzyme, a dipeptidyl carboxypeptidase located in the vascular endothelium, releases the C-terminal dipeptide His-Leu from angiotensin I to generate the active octapeptide angiotensin II (3–6), which is finally inactivated by angiotensinases. Angiotensin II exhibits a broad spectrum of biological activities, but among these the most significant property is its powerful vasoconstricting effect. Although the role of angiotensin converting enzyme in the generation of angiotensin II and, thereby, in the control of blood pressure has long been recognized, its clinical importance has only recently been highlighted by the discovery that specific inhibitors of this enzyme are potential drugs for the control of hypertension in man (7).