STRUCTURAL FEATURES OF HUMAN CYTOCHROME P450 7B1 WITH AN AMINO ACID SUBSTITUTION OF Phe470Ile
https://doi.org/10.29235/1561-8323-2018-62-4-423-431
Abstract
To study the influence of the amino acid substitution of Phe470Ile, correlating with the spastic paraplegia of type 5, on the structure of human cytochrome P450 7B1, the spatial full-atomic models of this enzyme and its mutant form were created. It was found that Phe470 does not influence directly the catalytic properties of the enzyme because of its localization far from the active site. It was shown that the residue under investigation belongs to a highly conservative region of the protein structure and can influence the CYP7B1 correct folding. In particular, the amino acid substitution of Phe470Ile increases rigidity and stability of sterol 7α-hydroxylase. This can be a reason of changes in the CYP7B1 hydroxylase activity in relation to neurosteroids.
Keywords
human cytochrome P450 7B1 (CYP7B1),
spastic paraplegia type 5,
accelerated molecular dynamics,
stability of protein structure,
principal component analysis
Supporting agencies: Authors acknowledge M. A. Shapira for assistance in analyzing the data obtained.
About the Authors
Yaraslau V. Dzichenka
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Dzichenka Yaraslau Uladzimiravich – Ph. D. (Chemistry), Senior Research
5/2, Kuprevich Str., 220141, Minsk
Eugene S. Gudny
Belarusian State University
Belarus
Belarus
Gudnyy Eugene Sergeevich – Student
10, Kurchatov Str., 220045, Minsk
Sergei A. Usanov
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Usanov Sergei Aleksandrovich – Corresponding Member, D. Sc. (Chemistry), Professor
5/2, Kuprevich Str., 220141, Minsk
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