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Energy profiles of the catalytic cycle of enzymatic reactions and factors determining enzymatic catalysis efficiency

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Abstract

Free energy profiles along the reaction coordinate were analyzed for several model systems by modeling elementary processes of the catalytic cycle of enzymes. A substantial contribution of fast non-limiting steps, which are conformational changes/adjustments, and proton transfer steps to the implementation of the catalytic cycle and high rates of enzymatic reactions is shown. The rate constants of conformational changes and proton transfer steps were determined from an analysis of the free energy profiles. In most cases, the lifetimes of the conformers lie in a range of 10−10 s. A distinctive feature of enzymatic catalysis is the multistep character of the reactions, while the catalytic cycle is accomplished in the conformationally flexible polymer matrix with the conformational adjustment of the active site of the enzyme.

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Authors and Affiliations

  1. Department of Chemistry, Lomonosov Moscow State University, Build. 3, 1 Leninskie Gory, 119991, Moscow, Russian Federation

    S. D. Varfolomeev, A. V. Nemukhin, M. G. Khrenova & B. L. Grigorenko

  2. N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4 ul. Kosygina, 119334, Moscow, Russian Federation

    S. D. Varfolomeev, A. V. Nemukhin & B. L. Grigorenko

  3. Institute of Physicochemical Foundations of Functioning of Neuronal Networks and Artificial Intelligence, Lomonosov Moscow State University, Build. 3, 1 Leninskie Gory, 119991, Moscow, Russian Federation

    S. D. Varfolomeev & A. V. Nemukhin

  4. A. N. Bach Institute of Biochemistry, Russian Academy of Sciences, Federal Research Center of Biotechnology of the Russian Academy of Sciences, 33 Leninsky prosp., 119071, Moscow, Russian Federation

    M. G. Khrenova

Authors
  1. S. D. Varfolomeev
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  2. A. V. Nemukhin
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  3. M. G. Khrenova
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  4. B. L. Grigorenko
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Corresponding author

Correspondence to A. V. Nemukhin.

Additional information

Dedicated to Academician of the Russian Academy of Sciences I. P. Beletskaya on the occasion of her anniversary.

Modeling of the chemical reaction mechanisms was performed using equipment of the Center for Collective Use of Supercomputational Resources of the Moscow State University.

This work was financially supported by the Russian Science Foundation (Project No. 22-13-00012, M. G. Khrenova and B. L. Grigorenko).

No human or animal subjects were used in this research.

The authors declare no competing interests.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, Vol. 72, No. 3, pp. 617–623, March, 2023.

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Varfolomeev, S.D., Nemukhin, A.V., Khrenova, M.G. et al. Energy profiles of the catalytic cycle of enzymatic reactions and factors determining enzymatic catalysis efficiency. Russ Chem Bull 72, 617–623 (2023). https://doi.org/10.1007/s11172-023-3825-7

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  • DOI: https://doi.org/10.1007/s11172-023-3825-7

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