Structure of 50S precursor bound methyltrasferase and sinefungin

The onset of antimicrobial resistance is primarily brought about by the overuse and misuse of antibiotics. Among the various ways microbes develop resistance, target modification offers a convenient and efficient way via which pathogens can bypass the effect of these drugs. Target alteration can result from the spontaneous mutation of a bacterial gene or can be mediated via modifying enzymes. Erythromycin resistance methyltransferases (Erms) is an example of the latter and specifically mono/dimethylates the 23S ribosomal RNA (rRNA). Methylation of the target site by Erms helps the pathogens to develop resistance to several classes of drug moieties, i.e., the macrolide, lincosamide, and streptogramin B families. The structure of the 50S precursor-Erm complex will help to delineate the rRNA and protein structure-based determinants determinants that facilitate such a specific catalytic process.