Steitz's group used ribosomal subunits from the primitive archaebacterium Haloarcula marismortui (Hma), which is found in the Dead Sea. They chose Hma ribosomes for their studies because they crystallize well enough to yield high-resolution structural data, but these ribosomes, like those from eukaryotes, are resistant to most MLSBK antibiotics.
The researchers analyzed the structure of erythromycin ?among the most widely prescribed macrolide antibiotics ?bound to a mutated version of the Hma ribosome that corresponds to a form found in pathogenic bacteria. Their studies revealed details of erythromycin binding to the mutant form of the Hma ribosome that do not agree with similar analyses by other researchers, according to Steitz. The studies by Steitz's group yielded new information about the basic chemical principles that underlie binding of the antibiotic to the ribosome, as well as new data about how that mutation confers drug resistance.
Steitz and his colleagues also analyzed the structure of five other clinically important antibiotics ?azithromycin, telithromycin, clindamycin, and virginiamycin M and virginiamycin S ?bound to the large mutated ribosomal subunit. Steitz said these studies provided new details about the nature of drug resistance involving these antibiotics. Furthermore, the studies of the two forms of virginiamycin offer an explanation for how the two forms of that antibiotic work synergistically to kill bacteria.
Finally, the researchers used x-ray crystallography to explore at high resolution the structural basis of a particular ribosomal mutation dubbed L22 that confers resistance to macrolides such as erythromycin. In a se
Source:Howard Hughes Medical Institute