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Федеральное государственное бюджетное учреждение науки
Институт теоретической и экспериментальной биофизики
Российской академии наук


ООО "ИЦ КОМКОН"

Адрес редакции и реквизиты

192012, Санкт-Петербург, ул.Бабушкина, д.82 к.2, литера А, кв.378

ISSN 1999-6314


Фундаментальные исследования • Фармакология

Том: 24
Статья: « 97 »
Страницы:. 1450-1483
Опубликована в журнале: 21 ноября 2023 г.
English version

Гамка-рецептор как мишень для разработки новых лекарственных средств

Иванов И.М., Орлова А.Б., Никифоров А.С., Карташев В.А., Юдин М.А., Чепур С.В.
1 ФГБУ Государственный научно-исследовательский испытательный институт военной медицины Министерства обороны Российской Федерации,
195043, г. Санкт-Петербург, ул. Лесопарковая, д. 4
e-mail: gniiivm_15@mil.ru
2 ФГБОУ ВО Северо-Западный государственный медицинский университет им. И.И. Мечникова Минздрава Российской Федерации,
195067, г. Санкт-Петербург, Пискаревский проспект, д. 47
e-mail: rectorat@szgmu.ru


Резюме
В обзоре рассмотрены строение, функционирование и особенности сайтов связывания лигандов с рецептором гамма-аминомасляной кислоты типа А (далее ГАМКАР) во внеклеточном и трансмембранном домене рецептора. Проанализированы доступные комплексы ГАМКАР с ортосетрическими агонистами (ГАМК, THIP, гистамин) и антагонистами (бикукуллин), лигандами бензодиазепинового сайта (золпилем, диазепам, DMCD, флумазенил и Ro154513), барбитуратного сайта (фенобарбитал), сайтов общих анестетиков (этомидат, пропофол) и нейростероидами. Проведен частотный анализ паттернов взаимодействия этих лигандов с аминокислотными остатками мишеней и сравнение особенностей взаимодействия с ними агонистов и антагонистов. Визуализованы области связывания лигандов разных типов и оценено их взаиморасположение на рецепторе. Оценена возможность использования доступных трехмерных моделей ГАМКАР в качестве мишеней для поиска новых лигандов с ГАМКергической активностью методами молекулярного моделирования и докинга.


Ключевые слова
ГАМК, ГАМКА-рецептор, сайт связывания, бензодиазепины, барбитураты, общие анестетики, нейростероиды.


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