Aminoglycosides are one of the most widely used and clinically important classes
of antibiotics that target the ribosome. Hygromycin B is an atypical
aminoglycoside antibiotic with unique structural and functional properties. Here
we describe the structure of the intact Escherichia coli 70S ribosome in complex
with hygromycin B. The antibiotic binds to the mRNA decoding center in the small
(30S) ribosomal subunit of the 70S ribosome and induces a localized
conformational change, in contrast to its effects observed in the structure of
the isolated 30S ribosomal subunit in complex with the drug. The conformational
change in the ribosome caused by hygromycin B binding differs from that induced
by other aminoglycosides. Also, in contrast to other aminoglycosides, hygromycin
B potently inhibits spontaneous reverse translocation of tRNAs and mRNA on the
ribosome in vitro. These structural and biochemical results help to explain the
unique mode of translation inhibition by hygromycin B.
