The study of interaction of N–(L–histidyl) chloramphenicolamine with non-canonical binding site of chloramphenicol with MD simulations

Авторы: Makarov G.I., Kosareva K.A.
Сборник: AIP Conference Proceedings
Том: 2390
Год издания: 2022
Место издания: AIP Publishing
Номер статьи: 020044
DOI: 10.1063/5.0069213
Аннотация: N–(L–Histidyl) chloramphenicolamine (L–HisCam), a derivative of the antibiotic chloramphenicol, binds to the vacant E. coli ribosome by an order of magnitude stronger than chloramphenicol, but inhibits protein biosynthesis in vitro many times weaker. It has been known that chloramphenicol can bind to a non-canonical binding site occurring in the E. coli ribosome when it is in the canonical A,A/P,P–state. Binding the ribosome in this way, chloramphenicol can interact with a nascent peptide. In the present work, we studied the interaction of L–HisCam with the non-canonical chloramphenicol binding site and revealed that the compound can bind to this site forming stable stacking interactions and hydrogen bonds. However, in this case the L–histidine residue of L–HisCam interacts intensively with the nucleotide residues of the peptidyl transferase center, leaving the lumen of the nascent peptide exit tunnel and therefore being unable to interact with the nascent peptide. This observation explains the reduced inhibitory activity of L–HisCam.
Добавил в систему: Макаров Геннадий Иванович

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