Mixed-type inhibition of bovine lung angiotensin converting enzyme by lisinopril and its dansyl derivative.
The steady-state inhibition of bovine lung angiotensin converting enzyme (ACE; EC 3.4.15.1) by the slow-binding inhibitor lisinopril and its dansyl derivative conformed to a linear mixed inhibition model with inhibitor binding to ES as well as to E. Studied at pH8, 35 degrees, and using N-(3-[2-furyl]-acryloyl)phe-gly-gly as substrate, the approach to steady-state activity at different substrate concentrations pointed to slow isomerizations in both EI and EIS. While an inhibitory scheme involving a single I-binding site adequately accounts for the data presented, information relating to the primary structure of ACE brings up a two-site alternative which remains to be tested.
Uçar
G
G
Department of Biochemistry, School of Pharmacy, Hacettepe University, Ankara, Turkey.
Ozer
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I
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003619:Dansyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D007536:Isomerism; D007700:Kinetics; D017706:Lisinopril; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D009842:Oligopeptides / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry* / Q000302:isolation & purification
D000806:Angiotensin-Converting Enzyme Inhibitors; D003619:Dansyl Compounds; D004151:Dipeptides; D009842:Oligopeptides; C038275:2-furanacryloyl-phenylalanyl-glycyl-glycine; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A