Penicillin-binding proteins: evergreen drug targets

The penicillin-binding proteins (PBPs) are well known targets for the β-lactam antibiotics. They continue to be a focus of interest for pharmaceutical design, as exemplified by the number of new agents under clinical investigation as well as novel experimental molecules. Considerable advances have been made in understanding the structure and function of this family of enzymes, through high-resolution structural studies and mechanistic studies in solution. These studies have thrown light on role of the high molecular mass PBPs in mediating β-lactam resistance, although much work remains to be done to enable a full description of the mechanisms by which these proteins modulate their sensitivity towards β-lactams while retaining their essential activity in cell wall biosynthesis.