Prof Ada Yonath
Prof Ada Yonath
*Department of Structural Biology, Weizmann Institute, Rehovot, Israel
Ribosomes, the universal cellular machines for the translation of the genetic code, possess spectacular architecture accompanied by inherent mobility that allows for their smooth performance as polymerases. The site for peptide bond formation (PTC) is located within a universal internal symmetrical region connecting all of the remote ribosomal features involved in its functions. The elaborate architecture of this region positions ribosomal substrates in appropriates stereochemistry for peptide bond formation, for substrate-mediated catalysis, and for substrate translocation. The high conservation of the symmetrical region implies its existence irrespective of environmental conditions and indicates that it represents the ancient ribosome. The PTC is located above an elongated tunnel along which nascent chains progress until they emerge out of the ribosome. This tunnel may also be involved in chaperoning function, provides the binding site of the first cellular chaperone that encounters the emerging nascent chain, and hosts a major family of antibiotics.
Crystallographic analysis of complexes of ribosomes and antibiotics targeting them revealed the structural bases for synergism, selectivity, induced fit; remote interactions, secondary conformational rearrangements and cross-resistance to ribosomal antibiotics; the common and specific pathways of resistance and cross resistance; the minute chemical differences that can turn competition into synergism; and the factors leading to resistance acquired by secondary conformational alterations.