RlmN and Cfr catalyze the methylation of adenosine 2503 of 23S rRNA at C-2 and C-8 position respectively. A2503 is located in peptidyl transferase center (PTC) of bacterial ribosome near the entrance to the exit channel for nascent peptide. C-8 modification by CFR plays a major role in antibiotic resistance that specifically target bacterial ribosome and breakdown protein synthesis machinery. In this research we are trying to understand the role two cysteines (Cys105, Cys338 for CFR and Cys118, Cys355 for RlmN) in the catalytic activity of CFR and RlmN. Our research established the role of two cysteines in the methyl group transfer from SAM to A2503 through a protein-RNA crosslinked radical intermediate and its conversion to final product. Currently, we are trying to understand the mechanism, which allows the enzyme to turnover from protein cross-linked intermediate to its fully active state.

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