Biochemistry Seminar: Squire Booker, Penn. State University
Wed, Mar 26
12:00 PM — 1:00 PM
MarshakCity College of New York
Marshak, MR 1027
Squire Booker, Prof., will give a talk on "A Radical Reaction Leading to Antibiotic Resistance"Squire Booker, Prof., Depts of Chemistry, and Biochemistry & Mol Biology, Penn. State Univ., "A Radical Reaction Leading to Antibiotic Resistance"
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. This seemingly minor modification, installed by the protein, Cfr, impedes the binding of over five classes of antibiotics to their ribosomal targets. Considering that almost one-half of all antibiotics currently in use target the bacterial ribosome, this emerging mechanism of resistance has the potential to greatly diminish the current arsenal of clinically relevant antibiotics. Although the appended methyl group derives from S-adenosylmethionine (SAM), C8 of adenosine is chemically resistant to the well established paradigm for how SAM is used to donate methyl groups. Cfr is a member of a growing superfamily of enzymes that use SAM to carry out chemical transformations via radical mechanisms. This lecture will detail a new and novel strategy for the biological methylation of sp2-hybridized carbon centers employed by Cfr, involving radical intermediates and the participation of five cysteine residues.