Biological implications of the ribosome's stunning stereochemistry.
The ribosome's striking architecture is ingeniously designed for its efficient polymerase activity in the biosynthesis of proteins, which is a prerequisite for cell vitality. This elaborate architecture is comprised of a universal symmetrical region that connects all of the ribosomal functional centers involved in protein biosynthesis. Assisted by the mobility of selected ribosomal nucleotides, the symmetrical region provides the structural tools that are required not only for peptide bond formation, but also for fast and smooth successive elongation of nascent proteins. It confines the path along which the A-tRNA 3'-end is rotated into the P-site in concert with the overall tRNA/mRNA sideways movement, thus providing the required stereochemistry for peptide bond formation and substrate-mediated catalysis. The extreme flexibility of the nucleotides that facilitate peptide bond formation is being exploited to promote antibiotic selectivity and synergism, as well as to combat antibiotic resistance.
Zimmerman
Ella
E
Department of Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel.
Yonath
Ada
A
D000596:Amino Acids / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D010455:Peptides