Penicillin-binding protein 4 (PBP4) (PBP4)

Penicillin-binding protein 4 (PBP4) in Bacillus cereus is a low-molecular-weight (LMW) enzyme that functions as a D-alanyl-D-alanine carboxypeptidase. It is encoded by the dacB gene and is integral to the synthesis and maintenance of the bacterial peptidoglycan layer, specifically by removing the terminal D-alanine from pentapeptide side chains to regulate cross-linking. In Bacillus species, PBP4 is particularly significant during sporulation, where it contributes to the proper formation of the spore cortex, a structure necessary for environmental resilience. Because of its essential role in cell wall integrity, PBP4 serves as a target for various beta-lactam antibiotics, which inhibit the enzyme by forming a covalent bond with its active-site serine. Targeting PBP4 is a key strategy in treating infections caused by Bacillus cereus, an opportunistic pathogen known for causing foodborne illness and serious non-gastrointestinal infections.

Beta-lactam antibiotics act as substrate analogs that covalently bind to the active-site serine of Penicillin-binding protein 4, inhibiting its DD-carboxypeptidase activity and disrupting peptidoglycan maturation.