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Calorimetric analysis of lisinopril binding to angiotensin I-converting enzyme

Authors
Journal
FEBS Letters
0014-5793
Publisher
Wiley Blackwell (John Wiley & Sons)
Publication Date
Volume
423
Issue
1
Identifiers
DOI: 10.1016/s0014-5793(98)00069-6
Keywords
  • Angiotensin I-Converting Enzyme
  • Lisinopril
  • Microcalorimetry
  • Binding
Disciplines
  • Biology

Abstract

Abstract 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.

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