danДоклады Национальной академии наук БеларусиDoklady of the National Academy of Sciences of Belarus1561-83232524-2431The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8323-2018-62-4-423-431dan-536Research ArticleХИМИЯCHEMISTRYСТРУКТУРНЫЕ ОСОБЕННОСТИ ЦИТОХРОМА P450 7B1 ЧЕЛОВЕКА С АМИНОКИСЛОТНОЙ ЗАМЕНОЙ Phe470IleSTRUCTURAL FEATURES OF HUMAN CYTOCHROME P450 7B1 WITH AN AMINO ACID SUBSTITUTION OF Phe470IleДиченкоЯ. В.DzichenkaYaraslau V.

Диченко Ярослав Владимирович – канд. хим. наук, ст. науч. сотрудник

ул. Купревича, 5/2, 220141, Минск

Dzichenka Yaraslau Uladzimiravich – Ph. D. (Chemistry), Senior Research

5/2, Kuprevich Str., 220141, Minsk

dichenko@iboch.byГудныйЕ. С.GudnyEugene S.

Гудный Евгений Сергеевич – студент

ул. Курчатова, 10, 220045, Минск

Gudnyy Eugene Sergeevich – Student

10, Kurchatov Str., 220045, Minsk

etry@list.ruУсановС. А.UsanovSergei A.

Усанов Сергей Александрович – член-корреспондент, д-р хим. наук, профессор

ул. Купревича, 5/2, 220141, Минск

Usanov Sergei Aleksandrovich – Corresponding Member, D. Sc. (Chemistry), Professor

5/2, Kuprevich Str., 220141, Minsk

usanov@iboch.basnet.byИнститут биоорганической химии Национальной академии наук БеларусиInstitute of Bioorganic Chemistry of the National Academy of Sciences of BelarusБелорусский государственный университетBelarusian State University201812092018624423431Copyright © Диченко Я.В., Гудный Е.С., Усанов С.А., 20182018Диченко Я.В., Гудный Е.С., Усанов С.А.Dzichenka Y.V., Gudny E.S., Usanov S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://doklady.belnauka.by/jour/article/view/536

С целью изучения влияния аминокислотной замены Phe470Ile, коррелирующей с возникновением спастической параплегии типа 5, на пространственную структуру цитохрома P450 7B1 человека построены компьютерные модели данного фермента и его варианта с соответствующей мутацией. Установлено, что Phe470 не влияет напрямую на каталитические свойства фермента в силу того, что он локализован далеко от активного центра фермента. Однако расположение 470 остатка в высоко консервативной области белка свидетельствует о его важной роли в формировании корректной пространственной структуры исследуемой стероид 7α-гидроксилазы. В частности, аминокислотная замена Phe470Ile приводит к увеличению жесткости и, как следствие этого, стабильности пространственной структуры CYP7B1, что может являться причиной изменения профиля гидроксилазной активности фермента по отношению к нейростероидам.

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.

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The authors declare that there are no conflicts of interest present.