Enthalpy of captopril‐angiotensin I‐converting enzyme binding

FEBS Letters

Ortiz-Salmerón, Emilia¹  Garcı́a-Fuentes, Luis¹  Barón, Carmen¹ 

[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;    Captopril;    Microcalorimetry;    Binding;    ACE;    angiotensin I-converting enzyme;    Cacodylate;    cacodylic acid;    MES;    2-(N-morpholino)ethanesulfonic acid;    Aces;    2-[(2-amino-2-oxoethyl)amino]ethanesulfonic acid;    FAPGG;    2-furanacryloyl-l-phenylalanyl glycyl-glycine;    ITC;    isothermal titration calorimetry;    Captopril;    d-[3-mercapto-2-methylpropanoyl]-l-proline;   

DOI  :  10.1016/S0014-5793(98)01075-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

High-sensitivity titration calorimetry is used to measure changes in enthalpy, heat capacity and protonation for the binding of captopril to the angiotensin I-converting enzyme (ACE; EC 3.4.15.1). The affinity of ACE to captopril is high and changes slightly with the pH, because the number of protons linked to binding is low. The determination of the enthalpy change at different pH values suggests that the protonated group in the captopril-ACE complex exhibits a heat protonation of approximately −30 kJ/mol. This value agrees with the protonation of an imidazole group. The residues which may become protonated in the complex could be two histidines existing in two active sites, which are joined to the amino acids coordinated to Zn²⁺. Calorimetric measurements indicate that captopril binds to two sites in the monomer of ACE, this binding being enthalpically unfavorable and being dominated by a large positive entropy change. Thus, binding is favored by both electrostatic and hydrophobic interactions. The temperature dependence of the free energy of binding ΔG° is weak because of the enthalpy-entropy compensation caused by a large heat capacity change, ΔC _p=−4.3±0.1 kJ/K/mol of monomeric ACE. The strong favorable binding entropy and the negative ΔC _p indicate both a large contribution to binding due to hydrophobic effects, which seem to originate from dehydration of the ligand-protein interface, and slight conformational changes in the vicinity of the active sites.

【 授权许可】

Unknown