Thiacalix[4]arenes Remove the Inhibitory Effects of Zn Cations on the Myosin ATPase Activity

Numerous female reproductive abnormalities are caused by uterine smooth muscle (myometrium) disorders. Heavy metals have an adverse effect on the contractility of the uterine smooth muscle. Although zinc is an essential biogenic element for most of the organisms, high doses of this element are toxic. The study of 0.5-5 mM Zn²⁺ effect on myosin S1 ATPase activity from the uterus found that 5 mM Zn²⁺ cations have the most pronounced inhibitory effect. The calculation of the kinetic parameters (K_m and V_max, _ATP) revealed that the apparent maximum velocity of the hydrolysis ATP catalyzed by myosin in the presence of 5 mM Zn²⁺ decreased by 1.6 times. The value of К_m for ATP hydrolysis by myosin S1 in the presence of Zn²⁺ does not change statistically, although it tends to decrease. It was determined that uterine myosin S1 ATPase activity does not depend on the concentration of Mg²⁺ in the presence of 5 mM Zn²⁺. Also, it was demonstrated that tetrahydroxythiacalix[4]arene-tetrasulfosphonate (C-798) and tetrahydroxythiacalix[4]arene-tetraphosphonate (C-800) restored myosin S1 ATPase activity to the control level in the presence of 5 mM Zn²⁺. One of the most probable mechanisms of restoring the action of these thiacalix[4]arenes protective effect is based on its ability to chelate heavy metal cations from the incubation medium. The molecular docking of C-798 and C-800 into the myosin S1 region showed that these thiacalix[4]arenes could interact with Zn cation bond by myosin amino acid residues near the ATPase active site. Therefore, thiacalix[4]arenes may weaken the interaction between this cation and myosin S1. It was speculated that the obtained results could be used for further research with the aim of using this thiacalix[4]arenes as pharmacological compounds in the case of poisoning with high concentrations of zinc.