Virtual screening and experimental verification to identify potential inhibitors of the ErmC methyltransferase responsible for bacterial resistance against macrolide antibiotics.

Methyltransferases from the Erm family catalyze S-adenosyl-L-methionine-dependent modification of a specific adenine residue in bacterial 23S rRNA, thereby conferring resistance to clinically important macrolide, lincosamide, and streptogramin B antibiotics. Thus far, no inhibitors of these enzymes have been identified or designed that would effectively abolish theresistance in vivo. We used the crystal structure of ErmC’ methyltransferase as a target for structure-based virtual screening of a database composed of 58,679 lead-like compounds.

Marcin Feder, Elzbieta Purta, Lukasz Koscinski, Sonja Cubrilo, Gordana Maravis Vlahovicek, Janusz Bujnicki
February 1, 2008
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