Structure of the Ribosomes

The interpretation of the genetic code and formation of functional proteins is performed by the ribosome. Structural studies of both ribosomal subunits revealed the specific interactions between the ribosome and its substrates. The results show, that ribosomes do not actively catalyse peptid bond formation, but rather position the substrate accurately, which facilitates and accelerates a thermodynamically favored reaction. Crucial for this mechanism is the internal symmetry within the catalytic core, which precisely reflects the symmetry of the substrates. Its universality makes the ribosome an attractive target for a large number of structurally diverse antibiotics. Almost all antibiotics targeting the large ribosomal subunit, bind in the same region: either directly in the peptidyl transferase center directly inhibiting peptide bond formation; or at the entrance of the ribosomal tunnel inhibiting elongation of the nascent protein. The most recent studies of such ribosome-antibiotic complexes revealed the inhibitory mechanism of two streptogramins. These compounds attack both sites simultaneously and in a synergistic manner, which induces a rather stable alteration of the peptidyl transferase center. The detailed knowledge of the specific interactions between different classes of antibiotics and the ribosome might facilitate and accelerate the development of urgently desired new drugs.