TY - JOUR
T1 - Metallobacitracins: Affinity and structural study in aqueous solution
AU - Rodríguez-Uribe, Nadia Alejandra
AU - Pérez-González, Refugio
AU - Domínguez-Mendoza, Blanca Eda
AU - Medrano, Felipe
AU - Godoy-Alcántar, Carolina
PY - 2019
Y1 - 2019
N2 - Metallobacitracins are complexes with an extensive antimicrobial and biological activity. In this work, we investigated the metal complexation of bacitracin with several divalent metal ions in aqueous solution. The binding constants of Zn(2+), Cd(2+), Hg(2+), Cu(2+), Ni(2+), Pd(2+), Fe(2+), Mn(2+) and Mg(2+) to bacitracin were measured by UV/Vis spectroscopy, isotermic titration calorimetry (ITC) and potentiometry while the complexes were studied by Circular Dichroism and Nuclear Magnetic Resonance (15N HSQC) for Zn(2+), Cd(2+) and Hg(2+) at different pH. By UV/Vis spectroscopy the affinity is in the range 104 to 105 M−1 at pH 6 and follows the order Ni(2+) > Cd(2+) > Hg(2+) > Zn(2+) > Fe(2+). By potentiometry, the binding constants were determined in the pH range 2–12. Microcalorimetry shows that the stoichiometry of metallobacitracins investigated is 1:1 with binding constants in the range 105–102 M−1 at pH 6 and with an order of stability of Ni(2+) > Cd(2+) > Zn(2+) > Hg(2+); ΔS, ΔH and ΔG parameters were also determined. NMR spectroscopy lets us establish the binding site of the metal ion when comparing 15N HSQC of free bacitracin and complex in natural abundance; these findings agree with calorimetric results. Chemical shift changes in complexes containing Zn(2+) and Cd(2+) exhibit a similar behavior despite pH differences. Conversely, there is not a significant change for Hg(2+) complex. The obtained data contribute to understand the mechanism of the biological activity of the metallobacitracins and give the guideline for the design of more powerful metalloantibiotics.
AB - Metallobacitracins are complexes with an extensive antimicrobial and biological activity. In this work, we investigated the metal complexation of bacitracin with several divalent metal ions in aqueous solution. The binding constants of Zn(2+), Cd(2+), Hg(2+), Cu(2+), Ni(2+), Pd(2+), Fe(2+), Mn(2+) and Mg(2+) to bacitracin were measured by UV/Vis spectroscopy, isotermic titration calorimetry (ITC) and potentiometry while the complexes were studied by Circular Dichroism and Nuclear Magnetic Resonance (15N HSQC) for Zn(2+), Cd(2+) and Hg(2+) at different pH. By UV/Vis spectroscopy the affinity is in the range 104 to 105 M−1 at pH 6 and follows the order Ni(2+) > Cd(2+) > Hg(2+) > Zn(2+) > Fe(2+). By potentiometry, the binding constants were determined in the pH range 2–12. Microcalorimetry shows that the stoichiometry of metallobacitracins investigated is 1:1 with binding constants in the range 105–102 M−1 at pH 6 and with an order of stability of Ni(2+) > Cd(2+) > Zn(2+) > Hg(2+); ΔS, ΔH and ΔG parameters were also determined. NMR spectroscopy lets us establish the binding site of the metal ion when comparing 15N HSQC of free bacitracin and complex in natural abundance; these findings agree with calorimetric results. Chemical shift changes in complexes containing Zn(2+) and Cd(2+) exhibit a similar behavior despite pH differences. Conversely, there is not a significant change for Hg(2+) complex. The obtained data contribute to understand the mechanism of the biological activity of the metallobacitracins and give the guideline for the design of more powerful metalloantibiotics.
KW - Bacitracin
KW - Divalent metal
KW - Binding constants
KW - Metallobacitracins
U2 - 10.1016/j.inoche.2019.03.035
DO - 10.1016/j.inoche.2019.03.035
M3 - Artículo
VL - 104
SP - 61
EP - 70
JO - Inorganic Chemistry Communications
JF - Inorganic Chemistry Communications
SN - 1387-7003
ER -