title: Penicillin and beyond: evolution, protein fold, multimodular polypeptides, and multiprotein complexes.
abstract: As the protein sequence and structure databases expand, the relationships between proteins, the notion of protein superfamily, and the driving forces of evolution are better understood. Key steps of the synthesis of the bacterial cell wall peptidoglycan are revisited in light of these advances. The reactions through which the D-alanyl-D-alanine depeptide is formed, utilized, and hydrolyzed and the sites of action of the glycopeptide and beta-lactam antibiotics illustrate the concept according to which new enzyme functions evolve as a result of tinkering of existing proteins. This occurs by the acquisition of local structural changes, the fusion into multimodular polypeptides, and the association into multiprotein complexes.
authors.affiliation: Centre d'Ingénierie des Protéines, Université de Liège, Sart Tilman, Belgium.
authors.forename: J M
authors.initials: JM
authors.lastname: Ghuysen
authors.forename: P
authors.initials: P
authors.lastname: Charlier
authors.forename: J
authors.initials: J
authors.lastname: Coyette
authors.forename: C
authors.initials: C
authors.lastname: Duez
authors.forename: E
authors.initials: E
authors.lastname: Fonzé
authors.forename: C
authors.initials: C
authors.lastname: Fraipont
authors.forename: C
authors.initials: C
authors.lastname: Goffin
authors.forename: B
authors.initials: B
authors.lastname: Joris
authors.forename: M
authors.initials: M
authors.lastname: Nguyen-Distèche
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005075:Biological Evolution; D002473:Cell Wall / Q000737:chemistry* / Q000378:metabolism; D010406:Penicillins / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D010406:Penicillins; D010455:Peptides