The structural basis for recognition and modification of the 30S ribosomal subunit by an antibiotic resistance methyltransferase (569.3)

Abstract

Ribosomal RNA contains modifications at specific nucleotides in all organisms, some of which control resistance to antibiotics. However, the mechanisms are not well understood controlling how modification enzymes recognize their specific target nucleotide and position it within the active site. We report the crystal structure of the pathogen‐derived aminoglycoside‐resistance rRNA methyltransferase NpmA bound to the 30S ribosomal subunit in a pre‐catalytic state. The structure reveals that NpmA recognizes conserved rRNA tertiary structure rather than RNA sequence. Additionally, the structure shows NpmA flips the target nucleotide from its position within the helical base stack to position it within the active site. The structure provides a general framework for investigating the mechanisms of other rRNA modification enzymes.Grant Funding Source: Supported by National Institutes of Health