Calorimetric analysis of lisinopril binding to angiotensin I‐converting enzyme

FEBS Letters

Garcı́a-Fuentes, Luis¹  Barón, Carmen¹  Téllez-Sanz, Ramiro¹ 

[1] Departamento de Quı́mica Fı́sica, Bioquı́mica y Quı́mica Inorgánica, Facultad de Ciencias Experimentales, Universidad de Almerı́a, La Cañada de San Urbano, 04120 Almerı́a, Spain

关键词: Angiotensin I-converting enzyme;    Lisinopril;    Microcalorimetry;    Binding;    ACE;    angiotensin I-converting enzyme;    Cacodylate;    cacodylic acid;    FAPGG;    2-furanacryloyl-l-phenylalanyl glycyl-glycine;    ITC;    isothermal titration calorimetry;    lisinopril;    N α-[(S)-1-carboxy-3-phenyl]-l-lysyl-l-proline;   

DOI  :  10.1016/S0014-5793(98)00069-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 ΔC_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 Zn²⁺ and lisinopril results in a higher affinity of the holoenzyme for this drug due to a more favorable entropic contribution.

【 授权许可】

Unknown