Abstract
Three-dimensional full-atom model of the enzyme complex with acetyl-CoA and substrate was constructed on the basis of the primary sequence of amino acid residues of N-acetyl glutamate synthase. Bioinformatics approaches of computer modeling were applied, including multiple sequence alignment, prediction of co-evolutionary contacts, and ab initio folding. On the basis of the results of calculations by classical molecular dynamics and combined quantum and molecular mechanics (QM/MM) methods, the structure of the active site and the reaction mechanism of N-acetylglutamate formation are described. Agreement of the structures of the enzyme–product complexes obtained in computer modeling and in the X-ray studies validates the reliability of modeling predictions.
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ACKNOWLEDGMENTS
The study was carried out using the equipment of the Ultra-High Performance Computing Resources Core Facility of Moscow State University, as well as the supercomputer center of the Russian Academy of Sciences. We are grateful to Ph.D. A.K. Shaitan for a helpful discussion of this work.
Funding
The study was supported by the Russian Science Foundation (project no. 18-13-00030).
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Translated by M. Batrukova
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Polyakov, I.V., Kniga, A.E., Grigorenko, B.L. et al. Computer Modeling of N-Acetylglutamate Synthase: From Primary Structure to Elemental Stages of Catalysis. Dokl Biochem Biophys 495, 334–337 (2020). https://doi.org/10.1134/S1607672920060125
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DOI: https://doi.org/10.1134/S1607672920060125