Premium
Calorimetric analysis of lisinopril binding to angiotensin I‐converting enzyme
Author(s) -
Téllez-Sanz Ramiro,
Garcı́a-Fuentes Luis,
Barón Carmen
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00069-6
Subject(s) - lisinopril , chemistry , enthalpy , isothermal titration calorimetry , isothermal microcalorimetry , heat capacity , enzyme , angiotensin converting enzyme , binding constant , entropy (arrow of time) , thermodynamics , biochemistry , binding site , endocrinology , biology , physics , blood pressure
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°C. Calorimetric measurements indicate that lisinopril binds to two sites in the monomer of both holo‐ 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 holo‐ and apo‐ACE, arising from a large heat capacity change of binding equal to −2.4±0.2 kJ/K/(mol of monomeric holo‐ACE) and to −1.9±0.2 kJ/K/(mol of monomeric apo‐ACE), respectively. The negative values of Δ C p for both systems are consistent with burial of a large non‐polar surface area upon binding. Although the binding of lisinopril to holo‐ and apo‐ACE is favored by entropy changes, this is more positive for the holoenzyme. Thus, the interaction between Zn 2+ and lisinopril results in a higher affinity of the holoenzyme for this drug due to a more favorable entropic contribution.