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Radical strategies for biological methylation
Author(s) -
Booker Squire J.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.258.3
Subject(s) - methylation , ribosome , chemistry , antibiotics , electrophile , nucleophile , ribosomal rna , methyltransferase , combinatorial chemistry , biochemistry , rna , catalysis , gene
A new and menacing mechanism for antibiotic resistance is on the rise, involving the C8 methylation of adenosine 2503 of 23S rRNA of the bacterial ribosome. Indeed, this seemingly minor addition, installed by the radical SAM protein, Cfr, impedes the binding of over five classes of antibiotics to their targets. Considering that one‐half of all antibiotics currently in use target the bacterial ribosome, this emerging mechanism of resistance has the potential to reduce the effectiveness of the world's current arsenal of antibiotics severely. Interestingly, C8 of adenosine is chemically resistant to biological methylation by all currently accepted mechanisms, which usually involves the attack of a nucleophile onto an electrophilic methylating agent. This lecture will detail a new and novel strategy for the biological methylation of sp 2 ‐hybridized carbon centers, which involves radical intermediates generated via the reductive cleavage of S‐adenosylmethionine and the participation of five essential cysteinyl residues. Support or Funding Information NIH GM 101957