The catalytic mechanism of angiotensin converting enzyme and related zinc enzymes.
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.
D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D008666:Metalloendopeptidases; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011817:Rabbits; D013379:Substrate Specificity
D002712:Chlorides; D010450:Endopeptidases; D007703:Peptidyl-Dipeptidase A; D008666:Metalloendopeptidases