Crystal structures of the 30S ribosomal subunit in complex with messenger R
NA and cognate transfer RNA in the A site, both in the presence and absence
of the antibiotic paromomycin, have been solved at between 3.1 and 3.3 ang
stroms resolution. Cognate transfer RNA (tRNA) binding induces global domai
n movements of the 30S subunit and changes in the conformation of the unive
rsally conserved and essential bases A1492, A1493, and G530 of 16S RNA. The
se bases interact intimately with the minor groove of the first two base pa
irs between the codon and anticodon, thus sensing Watson-Crick base-pairing
geometry and discriminating against near-cognate tRNA, The third, or "wobb
le," position of the codon is free to accommodate certain noncanonical base
pairs. By partially inducing these structural changes, paromomycin facilit
ates binding of near-cognate tRNAs.