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Crystal structure of Pseudomonas aeruginosa penicillin-binding protein 3 (PBP3) complexed with ceftobiprole
Structural highlights
FunctionFTSI_PSEAE Catalyzes cross-linking of the peptidoglycan cell wall at the division septum (By similarity). Binds penicillin (PubMed:20580675).[HAMAP-Rule:MF_02080][1] Publication Abstract from PubMedCeftobiprole is an advanced generation broad-spectrum cephalosporin antibiotic with potent and rapid bactericidal activity against Gram-positive pathogens including methicillin-resistant S. aureus (MRSA) as well as susceptible Gram-negative pathogens including Pseudomonas spp, pathogens. In the case of Pseudomonas aeruginosa ceftobiprole acts by inhibiting P. aeruginosa PBP3. Structural studies were pursued to elucidate the molecular details of this PBP inhibition. The crystal structure of the His-tagged PBP3:Ceftobiprole complex revealed a covalent bond between the ligand and the catalytic residue S294. Ceftobiprole binding leads to large active site changes near binding sites for the pyrrolidinone and pyrrolidine rings. The S528-L536 region adopts a conformation previously not observed in PBP3 including a partial unwinding of the alpha11 helix. These molecular insights can lead to a deeper understanding of beta-lactam:PBP interactions that result in major changes in protein structure as well as how to fine-tune current and develop novel inhibitors of this PBP. Structural insights into ceftobiprole inhibition of Pseudomonas aeruginosa penicillin-binding protein 3.,Kumar V, Tang C, Bethel CR, Papp-Wallace KM, Wyatt J, Desarbre E, Bonomo RA, van den Akker F Antimicrob Agents Chemother. 2020 Mar 9. pii: AAC.00106-20. doi:, 10.1128/AAC.00106-20. PMID:32152075[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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