Calorimetric analysis of lisinopril binding to angiotensin I-converting enzyme

Isothermal titration microcalorimetry has been used to measure changes in enthalpy and heat capacity for binding of lisinopril to the angiotensin I-converting enzyme (ACE; EC 3.4.15.1) and to its apoenzyme at pH 7.5 over a temperature range of 15-30 degrees C. Calorimetric measurements indicate that lisinopril binds to two sites in the monomer of both hole-and apo-ACE. Binding of lisinopril to both systems is enthalpically unfavorable and, thus, is dominated by a large positive entropy change, The enthalpy change of binding is strongly temperature-dependent for both hole-and ape-ACE, arising from a large heat capacity change of binding equal to -2.4 +/- 0.2 kJ/K/(mol of monomeric hole-ACE) and to -1.9 +/- 0.2 kJ/K/(mol of monomeric ape-ACE), respectively, The negative values of Delta C-p for both systems are consistent with burial of a large non-polar surface area upon binding. Although the binding of lisinopril to hole-and ape-ACE is favored by entropy changes, this is more positive for the holoenzyme, Thus, the interaction between Zn2+ and lisinopril results in a higher affinity of the holoenzyme for this drug due to a more favorable entropic contribution. (C) 1998 Federation of European Biochemical Societies.