The crystal structure of the complex of the large ribosomal subunit of the pathogen model Deinococcus radiodurans with the macrolide antibiotic methymycin, bearing a 12 membered macrolactone ring macrolide that contains a single amino sugar, shows that methymycin binds to the peptidyl transferase center (PTC) rather than to the high affinity macrolide binding pocket at the upper end of the ribosomal exit tunnel. This unexpected binding mode results in fairly efficient blockage of the 3’end of the A-site tRNA location, thus indicating the superiority of spatial-functional considerations over the formation of the typical high affinity macrolide interactions that due to the small size of methymycin could have led to incomplete blockage of the exit tunnel. Its binding involves rearrangements of several PTC nucleotides, some of which were shown previously to be flexible. Comparisons between the binding modes of methymycin and other antibiotics are presented and discussed.
Operational Program Digital Poland, 2014-2020, Measure 2.3: Digital accessibility and usefulness of public sector information; funds from the European Regional Development Fund and national co-financing from the state budget.
Feb 18, 2020
Jun 12, 2019
|Structural basis for the antibacterial activity of the 12-membered-ring mono-sugar macrolide methymycin||Feb 18, 2020|
Ziółkowski, Piotr Babula- Skowrońska, Danuta Kaczmarek, Małgorzata Cieśla, Agata Sadowski, Jan
Nowak, Jacek K.
Makowczyńska, Joanna Andrzejewska-Golec, Emilia Marek, Krystyna
Andrzejewska-Golec, Emilia Makowczyńska, Joanna Marek, Krystyna