Bacterial ribosomal RNA, with a complicated tertiary architecture, constitutes many functional sites in the ribosome. Therefore, it is a target for many antibiotics that inhibit the synthesis of bacterial proteins.
A class of antibiotics targeting ribosomal RNA are aminoglycosides. They are most active against aerobic Gram-negative bacteria and due to their possible oto- and nephrotoxicity are mainly used to treat severe hospital-acquired infections. The primary binding site of 2-deoxystreptamine aminoglycosides is located in the aminoacyl-tRNA binding site in the small ribosomal subunit. However, they were also found to bind to a neighbouring region in the large subunit.
I will describe our efforts to understand (thermo)dynamics of
aminoglycoside recognition by ribosomal RNA and the molecular
mechanism of aminoglycoside resistance due to RNA mutations and
enzymatic modification.