PENICILLIN AND BEYOND - EVOLUTION, PROTEIN FOLD, MULTIMODULAR POLYPEPTIDES, AND MULTIPROTEIN COMPLEXES

As the protein sequence and structure databases expand, the relationsh ips between proteins, the notion of protein superfamily, and the drivi ng forces of evolution are better understood, Key steps of the synthes is of the bacterial cell wall peptidoglycan are revisited in light of these advances. The reactions through which the D-alanyl-D-alanine dep eptide is formed, utilized, and hydrolyzed and the sites of action of the glycopeptide and beta-lactam antibiotics illustrate the concept ac cording to which new enzyme Functions evolve as a result of tinkering of existing proteins, This occurs by the acquisition of local structur al changes, the fusion into multimodular polypeptides, and the associa tion into multiprotein complexes.