416 ISSN 0006-3509, Biophysics, 2020, Vol. 65, No. 3, pp. 416–425. © Pleiades Publishing, Inc., 2020. Russian Text © The Author(s), 2020, published in Biofizika, 2020, Vol. 65, No. 3, pp. 493–503. Magnetic-Isotope Effects of Magnesium and Zinc in Enzymatic ATP Hydrolysis Driven by Molecular Motors V. K. Koltover a, *, R. D. Labyntseva b , and V. K. Karandashev c a Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow oblast, 142432 Russia b Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kiev, 01030 Ukraine c Institute of Microelectronics Technology and High Purity Materials, Russian Academy of Sciences, Chernogolovka, Moscow oblast, 142432 Russia *e-mail: koltover@icp.ac.ru Received November 30, 2019; revised March 4, 2020; accepted March 6, 2020 Abstract—The effects of different magnesium and zinc isotopes on the enzyme activity of myosin subfrag- ment-1 have been explored. The rate of the enzymatic ATP hydrolysis in reaction media enriched with the magnetic isotope, 25 Mg, is twice as high as it is in reaction media enriched with the nonmagnetic isotopes, 24 Mg or 26 Mg. A similar effect of nuclear spin catalysis has been detected in the experiments with zinc isotopes as cofactors of the enzyme. The rate of the enzymatic ATP hydrolysis with magnetic 67 Zn increases by 40– 50% compared to that with nonmagnetic 64 Zn or 68 Zn. The magnetic-isotope effects have been observed at the physiological concentration of magnesium and zinc chlorides (5 mM). The catalytic effect of the mag- netic magnesium isotope 25 Mg has been revealed in the experiments with Mg-dependent ATPase of myome- trial plasma membranes. The magnetic-isotope effects indicate that there is a spin-selective rate-limiting step in the chemo-mechanical process driven by the “molecular motor” due to the energy of ATP hydrolysis and that nuclear spin catalysis causes acceleration of this stage. Some possible mechanisms of the nuclear spin catalysis are discussed. Keywords: nuclear spin catalysis, myosin, ATPase activity, biomolecular motors, bioreliability, magnetic-iso- tope effect, magnesium, zinc DOI: 10.1134/S0006350920030094 INTRODUCTION Cells and tissues contain atoms of chemical ele- ments, many of which have two types of stable iso- topes, magnetic and nonmagnetic. As an example, magnesium has three stable isotopes, 24 Mg, 25 Mg, and 26 Mg with relative contents of 78.7, 10.1, and 11.2%, respectively. The 25 Mg isotope is magnetic because its atomic core has a nuclear spin (I = 5/2), which creates a magnetic field. The 24 Mg and 26 Mg isotopes are non- magnetic because their nuclei do not have a nuclear spin (I = 0) and, accordingly, do not create a magnetic field. Another common element in nature, zinc, has five stable isotopes, i.e., 64 Zn, 66 Zn, 67 Zn, 68 Zn, and 70 Zn with relative contents of 48.6, 27.9, 4.1, 18.8, and 0.6%, respectively. Among these, 67 Zn is the magnetic isotope (I = 5/2); the other four isotopes are nonmag- netic (I = 0). Magnetic isotopes are also known to cre- ate internal magnetic fields, which can exceed the Earth’s magnetic field (≈0.05 mT) by 10 to 100 times at a distance approximately equal to the chemical bond length [1]. Recently, magnetic isotope effects (MIE) were detected in experiments with living cells enriched with the magnesium magnetic isotope. As an example, the activity of the superoxide dismutase antioxidant enzyme in E. coli cells that were grown on a medium enriched with 25 Mg was lower by 40% than in cells grown on a medium enriched with the nonmagnetic isotope of magnesium [2]. S. cerevisiae yeast cells, enriched with the magnetic magnesium isotope, recover after irradiation with a short-wave ultraviolet light or ionizing radiation twice as fast as cells, enriched with the nonmagnetic magnesium isotope [3]. In the works of our group, the magnesium MIE was first detected in the reaction of ATP hydrolysis catalyzed by myosin, which is one of the most import- ant bioenergetic molecular motors [4, 5]. The goal of this work was to study the ATP-hydro- lase activity of biomolecular motors in the presence of various isotopes of magnesium and zinc as the cofac- tors of the enzyme. In experiments with myosin we revealed significant effects of the acceleration of enzy- matic hydrolysis in the presence of magnetic magne- sium and zinc isotopes in comparison with those in the presence of the nonmagnetic isotopes of the same Abbreviations: MIE, magnetic-isotope effect. MOLECULAR BIOPHYSICS