A calorimetric study of the binding of lisinopril, enalaprilat and captopril to angiotensin-converting enzyme.
The angiotensin I-converting enzyme (ACE; EC.3.4.15.1) is a dipeptidyl carboxypeptidase that plays a central role in blood pressure regulation. The somatic form of the enzyme is composed of two highly similar domains, usually referred to as N and C domains, each containing one active site. Nevertheless, a 1:1 stoichiometry for the binding of lisinopril, captopril or enalaprilat to somatic pig lung ACE is shown by isothermal titration calorimetry (ITC) and enzymatic assays. The binding of the three inhibitors at neutral pH is very tight and the enthalpy changes are positive, indicating that the binding is entropically driven. The origin of this thermodynamic signature is discussed under the new structural information available.
Andújar-Sánchez
M
M
Departamento Química Física, Bioquímica y Química Inorgánica, Universidad de Almería, Carretera Sacramento s/n, Almería 04120, Spain.
Cámara-Artigas
A
A
Jara-Pérez
V
V
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002151:Calorimetry; D002216:Captopril / Q000378:metabolism* / Q000494:pharmacology; D015773:Enalaprilat / Q000378:metabolism* / Q000494:pharmacology; D017706:Lisinopril / Q000378:metabolism* / Q000494:pharmacology; D008168:Lung / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D013552:Swine; D013816:Thermodynamics
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat