Multiple Modes of Zinc Binding to Histatin 5 Revealed by Buffer-Independent Thermodynamics.
Inorg Chem
; 62(18): 7087-7096, 2023 May 08.
Article
en En
| MEDLINE
| ID: mdl-37083393
ABSTRACT
Histatin 5 (Hist5) is an antimicrobial peptide found in human saliva as part of the innate immune system. Hist5 can bind several metal ions in vitro, and Zn2+ has been shown to function as an inhibitory switch to regulate the peptide's biological activity against the opportunistic fungal pathogen Candida albicans in cell culture. Here, we studied Zn2+ binding to Hist5 at four temperatures from 15 to 37 °C using isothermal titration calorimetry to obtain thermodynamic parameters that were corrected for competing buffer effects. Hist5 bound Zn2+ with a buffer-dependent association constant of â¼105 M-1 and a buffer-independent association constant of â¼6 × 106 M-1 at pH 7.4 and at all temperatures tested. Zn2+ binding was both enthalpically and entropically favorable, with larger entropic contributions at 15 °C and larger enthalpic contributions at 37 °C. Additionally, the ZnHist5 binding stoichiometry increased from 11 to 21 as temperature increased. The enthalpy-entropy compensation and the variable stoichiometry lead us to propose a model in which the Zn-Hist5 complex exists in an equilibrium between two distinct binding modes with different ZnHist5 stoichiometries. The in-depth thermodynamic analysis presented herein may help illuminate the biophysical basis for Zn-dependent changes in the antifungal activity of Hist5.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Histatinas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Inorg Chem
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos