danДоклады Национальной академии наук БеларусиDoklady of the National Academy of Sciences of Belarus1561-83232524-2431The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8323-2020-64-4-431-440dan-900Research ArticleХИМИЯCHEMISTRYIn silico анализ влияния фосфорилирования на структуру стероид-гидроксилаз человека CYP17A1 И CYP19A1In silico analysis of the phosphorylation effect on the structure of the human sterol-hydroxylases CYP17A1 AND CYP19A1ДиченкоЯ. В.DzichenkaYa. U.

Диченко Ярослав Владимирович - кандидат химических наук, старший научный сотрудник.

ул. Купревича, 5/2, 220141, Минск.

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.

dichenko@iboch.byТравкинаМ.TrawkinaM.

Травкина Мария - младший научный сотрудник.

ул. Купревича, 5/2, 220141, Минск.

Trawkina Maria - Junior researcher, Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus.

5/2, Kuprevich Str., 220141, Minsk.

maria_trawkina@iboch.byЯнцевичА. В.YantsevichA. V.

Янцевич Алексей Викторович - кандидат химических наук, заведующий лабораторией.

ул. Купревича, 5/2, 220141, Минск.

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.

al.yantsevich@gmail.comУсановС. A.UsanovS. A.

Усанов Сергей Александрович - член-корреспондент, доктор химических наук, профессор.

ул. Купревича, 5/2, 220141, Минск.

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.

usanov@iboch.byИнститут биоорганической химии Национальной академии наук БеларусиInstitute of Bioorganic Chemistry of the National Academy of Sciences of Belarus202030082020644431440Copyright © Диченко Я.В., Травкина М., Янцевич А.В., Усанов С.A., 20202020Диченко Я.В., Травкина М., Янцевич А.В., Усанов С.A.Dzichenka Y.U., Trawkina M., Yantsevich A.V., 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/900

С целью изучения влияния пост-трансляционных модификаций (ПТМ) на структуру и функции стероид-гидроксилаз человека CYP17A1 и CYP19A1 проведен анализ траекторий молекулярной динамики ферментов, содержащих модифицированные фосфогруппами аминокислотные остатки S258 (CYP17A1), T162 и Y361 (CYP19A1). Показано, что наличие ПТМ в структуре белка не приводит к значительным изменениям пространственной структуры ферментов и увеличивает общую стабильность белковой глобулы. Установлено, что фосфорилирование S258, T162 и Y361 оказывает влияние на интерфейс взаимодействия стероид-гидроксилаз с соответствующими донорами электронов путем уменьшения подвижности аминокислотных остатков, участвующих в формировании молекулярных комплексов с редокс-партнерами. Обнаружено, что фосфорилирование T162 (CYP19A1) приводит к уменьшению подвижности аминокислотных остатков, формирующих канал доступа субстрата в активный центр фермента. Полученные результаты проясняют механизм быстрой регуляции активности CYP17A1 и CYP19A1 человека посредством ПТМ.

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.

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