In silico analysis of the phosphorylation effect on the structure of the human sterol-hydroxylases CYP17A1 AND CYP19A1
https://doi.org/10.29235/1561-8323-2020-64-4-431-440
Abstract
The trajectories of molecular dynamics simulation of phosphorylated S258 (CYP17A1), T162 and Y361 (CYP19A1) were analyzed to understand a possible mechanism of influence of post-translational modification (PTM) on the structure and functions of human sterol-hydroxylases CYP17A1 and CYP19A1. It was found that PTM has no dramatic influence on the structures of the enzymes but stabilizes them. According to our data, the phosphorylation of S258, T162 and Y361 influences the interface of interaction between human sterol-hydroxylases and the corresponding electron donors by decreasing the mobility of amino acids that take part in forming molecular complexes of the enzymes and the corresponding redox-partners. The phosphorylation of T162 (CYP19A1) decreases the mobility of amino acids forming access channel. The obtained results can shed light on the mechanism of fast regulation of human CYP17A1 and CYP19A1 activity by PTM.
Supporting agencies: This work was supported by BRFFR: projects Х19-042 and X19M-093.
About the Authors
Ya. U. Dzichenka
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Dzichenka Yaraslau U. - Ph. D. (Chemistry), Senior researcher, Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus.
5/2, Kuprevich Str., 220141, Minsk.
M. Trawkina
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Trawkina Maria - Junior researcher, Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus.
5/2, Kuprevich Str., 220141, Minsk.
A. V. Yantsevich
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Yantsevich Aliaksei V. - Ph. D. (Chemistry), Head of the Laboratory, Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus.
5/2, Kuprevich Str., 220141, Minsk.
S. A. Usanov
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Usanov Sergei A. - Corresponding Member, D. Sc. (Chemistry), Professor, Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus.
5/2, Kuprevich Str., 220141, Minsk.
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