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Williams–Beuren syndrome-related methyltransferase WBSCR27: cofactor binding and cleavageстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 10 февраля 2021 г.
- Авторы: Mariasina S.S., Chang C.F., Petrova O.A., Efimov S.V., Klochkov V.V., Kechko O.I., Mitkevich V.A., Sergiev P.V., Dontsova O.A., Polshakov V.I.
- Журнал: FEBS Journal
- Том: 287
- Номер: 24
- Год издания: 2020
- Издательство: Blackwell Publishing Inc.
- Местоположение издательства: United Kingdom
- Первая страница: 5375
- Последняя страница: 5393
- DOI: 10.1111/febs.15320
- Аннотация: Williams-Beuren syndrome, characterized by numerous physiological and mental problems, is caused by the heterozygous deletion of chromosome region 7q11.23, which results in the disappearance of 26 protein coding genes. Protein WBSCR27 is a product of one of these genes whose biological function has not yet been established and for which structural information has been absent until now. Using NMR, we investigated the structural and functional properties of murine WBSCR27. For protein in the apo form and in a complex with S-(5'-adenosyl)-L-homocysteine (SAH), a complete NMR resonance assignment has been obtained and the secondary structure has been determined. This information allows us to attribute WBSCR27 to Class I methyltransferases. The interaction of WBSCR27 with the cofactor S-(5'-adenosyl)-L-methionine (SAM) and its metabolic products – SAH, MTA and 5'dAdo – was studied by NMR and isothermal titration calorimetry. SAH binds WBSCR27 much tighter than SAM, leaving open the question of cofactor turnover in the methylation reaction. One possible answer to this question is the presence of weak but detectable nucleosidase activity for WBSCR27. We found that the enzyme catalyzes the cleavage of the adenine moiety from SAH, MTA, and 5'dAdo, similar to the action of bacterial SAH/MTA nucleosidases. We also found that the binding of SAM or SAH causes a significant change in the structure of WBSCR27 and in the conformational mobility of the protein fragments, which can be attributed to the substrate recognition site. This indicates that the binding of the cofactor modulates the folding of the substrate-recognizing region of the enzyme.
- Добавил в систему: Польшаков Владимир Иванович