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Analysis of proton wires in the enzyme active site suggests a mechanism of c-di-GMP hydrolysis by the EAL domain phosphodiesterasesстатья
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: 4 декабря 2016 г.
- Авторы: Grigorenko Bella L., Knyazeva Marina A., Nemukhin Alexander V.
- Журнал: Proteins: Structure, Function and Bioinformatics
- Том: 84
- Номер: 11
- Год издания: 2016
- Издательство: Wiley-Liss Inc
- Местоположение издательства: United States
- Первая страница: 1670
- Последняя страница: 1680
- DOI: 10.1002/prot.25108
- Аннотация: We report for the first time a hydrolysis mechanism of the cyclic dimeric guanosine monophosphate (c-di-GMP) by the EAL domain phosphodiesterases as revealed by molecular simulations. A model system for the enzyme-substrate complex was prepared on the base of the crystal structure of the EAL domain from the BlrP1 protein complexed with c-di-GMP. The nucleophilic hydroxide generated from the bridging water molecule appeared in a favorable position for attack on the phosphorus atom of c-di-GMP. The most difficult task was to find a pathway for a proton transfer to the O3' atom of c-di-GMP to promote the O3'[BOND]P bond cleavage. We show that the hydrogen bond network extended over the chain of water molecules in the enzyme active site and the Glu359 and Asp303 side chains provides the relevant proton wires. The suggested mechanism is consistent with the structural, mutagenesis, and kinetic experimental studies on the EAL domain phosphodiesterases
- Добавил в систему: Немухин Александр Владимирович