Book of Abstracts: Albany 2005
NMR Studies of Ribosomal Stem-loop RNA Recognized by an erm Methyltransferase
Antibiotics are pivotal for the treatment of pathogenic bacterial infections. The inhibitory actions of a large number of antibiotics, amongst these the so-called MLS (macrolide, lincosamide, and streptogramin type-B) antibiotics, take place in the early stages of protein synthesis on the ribosome. The drug binds to the large (50S) subunit of bacterial ribosomes close to the peptidyl transferase center and sterically blocks the exit tunnel for the newly formed nascent polypeptide chain, thus preventing further protein growth and inducing dissociation of the peptidyl-tRNA from the ribosome. Many cases of MLS resistance can be linked to alterations of specific nucleotides in 23S RNA within the large ribosomal subunit. These alterations include single point mutations of nucleotides and enzymatic modification of the RNA at or in the vicinity of nucleotide position 2058 (1). Extensive molecular biological studies of 23S ribosomal RNA have unravelled the minimal RNA substrate that is recognized and methylated by the ErmE methyltransferase (2, 3). Methylation occurs at an adenosine analogous to the adenosine 2058 in ribosomal RNA. This minimal RNA substrate is a 27-mer stem-loop RNA oligonucleotide, in which there is a single-nucleotide bulge and an internal loop in the stem. These structural motifs appear to be critical for methylation by ErmE methyltransferase. We present results on the structural properties of this 27-mer RNA stem-loop oligonucleotide obtained with NMR spectroscopy.
References and Footnotes
Katrine E. Nielsen*
Nucleic Acid Center