Ribosome-chloramphenicol interactions: a nuclear magnetic resonance study

Proton magnetic resonance line broadening of chloramphenicol resonances has been employed to study the binding of this inhibitor of protein synthesis to the Escherichia coli 70 S ribosome. Temperature dependence measurements of the resonance line widths show that chloramphenicol is in fast exchange with the ribosome. Differential broadening of the various drug resonances suggests that it binds in its receptor site in essentially the same conformation that exists free in solution. Thus, even though the drug possesses a fair degree of structural flexibility, this is not necessary for its interaction with the ribosome. The recognition is most likely of the classic lock and key type, with the ribosomal site being essentially an open gate for the fitting of the drug. From the proton line-width measurements and ¹⁹F spectra of a derivative, it has been possible to propose a model for the geometry of chloramphenicol when it resides on the ribosome which is consistent with established structure-activity relationships for the drug.