Chapter 13. Bacterial Penicillin-Binding Proteins
1983; Elsevier BV; Linguagem: Inglês
10.1016/s0065-7743(08)60768-x
ISSN1557-8437
Autores Tópico(s)Biochemical and Structural Characterization
ResumoPublisher Summary Penicillin and other β-lactam antibiotics inhibit bacterial growth by binding to specific transpeptidases that crosslink peptidoglycan, the rigid bag-like macromolecule, responsible for the mechanical strength of the bacterial envelope. Penicillin acts as a steric analogue of the pentapeptide chain in growing peptidoglycan, forming a stable penicilloyl–enzyme complex with peptidoglycan transpeptidase. In contrary to the steric analogue model, penicillin acts as a transition-state analogue or a k cat inhibitor. Penicillin-binding protein (PBP) studies have significantly improved understanding of the mechanism of action of β-lactam antibiotics. At the cellular level, they have helped elucidate some of the processes involved in bacterial cell-wall biosynthesis and morphogenesis. At the molecular level, they have contributed to the understanding of intrinsic antibiotic activity and have provided the framework for structure–activity relationships. Penicillin-sensitive enzyme (PSE) studies have focused on DD-carboxypeptidases, non-essential PBPs that are plausible models for the interaction of penicillin with its targets. Together, PBP/PSE studies represent an approach to the rational design of the inhibitors of bacterial cell-wall biosynthesis. This chapter discusses the properties of PBPs in some of the better studied bacteria of clinical importance. The role of individual PBPs in bacterial susceptibility/resistance is also discussed in the chapter.
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