FEBS Letters | |
Calorimetric analysis of lisinopril binding to angiotensin I‐converting enzyme | |
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. | |
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【 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 ΔCp 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
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