The Catalytic Mechanism of Angiotensin Converting Enzyme and Related Zinc Enzymes

Abstract

Angiotensin converting enzyme (ACE) is one of a class of zinc peptidases that utilize glutamic acid as a catalytic residue. ACE also has important arginine and tyrosine residues that are involved in substrate binding and a lysine that binds chloride. Chloride activation of ACE depends on the particular substrate employed. It is an essential activator of class I substrates and a nonessential activator of class II substrates. Radiationless energy transfer using substrates labeled with the fluorescent dansyl group indicates that chloride promotes a two-step binding process. The second step is a change in protein conformation that can be monitored using fluorescent inhibitors. The chloride binding constant for the ACE-inhibitor complex at pH 7.5 is 2.2 mM.