The lack of rRNA structural changes in the A-site or in the decoding center suggest that the biochemical and phenotypic effects observed are indirectly due to the changes described above. The reciprocal effects between Ac-aa-tRNA binding with the P-site and aa-tRNA interactions with the A-site are intriguing. In the aa-tRNA binding reactions, the ribosomal P-sites were occupied with daeacylated tRNA. We suggest that in the 51-4A mutant, the P-site ligand is more 'locked' into a suboptimal conformation, which in turn feeds back to the A-site, resulting in decreased affinity for its ligand. Conversely, the lessened ability of 54-7A mutant ribosomes to lock P-site ligand in a suboptimal conformation may account for the increased affinity of these ribosomes for A-site ligand. Anisomycin resistance by both mutants also followed the reciprocal P-site/A-site pattern, i.e. both mutants were sparsomycin hypersensitive. Paromomycin interacts with the decoding center in the small subunit, where it promotes misreading of near-cognate codons in the A-site by stabilizing codon-anticodon interactions (45) . This sensitivity may be attributable to an observed increase in missense incorporation of a near cognate arginine (AGA) over that of the sense serine codon (AGC) in mutant 51-4A. Intriguingly, 54-7A had wild-type levels of missense incorporation suggesting that its sensitivity to paromomycin was indirect. The reciprocal anisomycin/paromomycin phenotypes of the L11 mutants demonstrate the effects of this protein on A-site ligand based ribosomal functions over very long distances. Similar phenotypic patterns were previously observed with mutants of other large subunit components (46, 47) .