6VJE

Crystal structure of Pseudomonas aeruginosa penicillin-binding protein 3 (PBP3) complexed with ceftobiprole

6VJE の概要

• エントリーDOI: 10.2210/pdb6vje/pdb
• 分子名称: Peptidoglycan D,D-transpeptidase FtsI, (2R)-2-[(1R)-1-{[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(hydroxyimino)acetyl]amino}-2-oxoethyl]-5-({2-oxo-1-[(3R)-pyr rolidin-3-yl]-2,5-dihydro-1H-pyrrol-3-yl}methyl)-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: antibiotic target, complex, hydrolase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 58936.94

構造登録者

van den Akker, F.,Kumar, V. (登録日: 2020-01-15, 公開日: 2020-03-11, 最終更新日: 2024-10-16)

主引用文献

Kumar, V.,Tang, C.,Bethel, C.R.,Papp-Wallace, K.M.,Wyatt, J.,Desarbre, E.,Bonomo, R.A.,van den Akker, F.
Structural Insights into Ceftobiprole Inhibition of Pseudomonas aeruginosa Penicillin-Binding Protein 3.
Antimicrob.Agents Chemother., 64:-, 2020

PubMed Abstract: Ceftobiprole is an advanced-generation broad-spectrum cephalosporin antibiotic with potent and rapid bactericidal activity against Gram-positive pathogens, including methicillin-resistant , as well as susceptible Gram-negative pathogens, including sp. pathogens. In the case of , ceftobiprole acts by inhibiting penicillin-binding protein 3 (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 to L536 region adopts a conformation previously not observed in PBP3, including partial unwinding of the α11 helix. These molecular insights can lead to a deeper understanding of β-lactam-PBP interactions that result in major changes in protein structure, as well as suggesting how to fine-tune current inhibitors and to develop novel inhibitors of this PBP.

PubMed: 32152075
DOI: 10.1128/AAC.00106-20

実験手法

X-RAY DIFFRACTION (1.76 Å)