As discussed above, the effects of the K237A mutant are locally confined to the PTC, while those conferred by R247A are more global. The latter is reflected in their different effects on ligand binding to the A-site: R247A promoted very strong effects on both aa-tRNA and eEF2 binding as compared to the much weaker effects conferred by K237A. Examination of the ligand binding data reveals a reciprocal relationship between affinities for aa-tRNA and eEF2, i.e. increased aa-tRNA K d correlates with decreased eEF2 K d (Figure 3 ). This is consistent with the model that L3 plays a central role as an allosteric switch to coordinate binding of elongation factors, opening and closing of the accommodation corridor, and PTC activity to ensure the unidirectionality of protein synthesis (13, 17) . Interestingly, all of the mutants affected peptidyltransfer, consistent with observations that this process is highly sensitive to even minor structural changes in the ribosome [reviewed in (63) ].