9SSH

PENICILLIN-BINDING PROTEIN 1B (PBP-1B) in complex with Ceftriaxone - Streptococcus pneumoniae R6

9SSH の概要

• エントリーDOI: 10.2210/pdb9ssh/pdb
• 関連するPDBエントリー: 9SSD 9SSE 9SSF 9SSG 9SSI
• 分子名称: Penicillin-binding protein 1B, CEFOTAXIME, C3' cleaved, open, bound form, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: cell wall, peptidoglycan synthesis enzyme, infection, drug-binding protein, antibiotics, transferase
• 由来する生物種: Streptococcus pneumoniae R6
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55334.18

構造登録者

Flanders, P.L.,Gillingham, J.R.,Contreras-Martel, C.,Dessen, A.,Carlson, E.E.,Ambrose, E.A. (登録日: 2025-09-25, 公開日: 2026-02-18)

主引用文献

Flanders, P.L.,Gillingham, J.R.,Contreras-Martel, C.,Dessen, A.,Carlson, E.E.,Ambrose, E.A.
Structural and Dynamics Analyses of beta-Lactam Inhibition of Streptococcus pneumoniae Penicillin-Binding Protein 1b (PBP1b) Guide Interrogation of Structure-Activity Relationships.
Acs Chem.Biol., 2026

PubMed Abstract: The Gram-positive pathogen , like the majority of bacteria, contains a peptidoglycan-based cell wall whose structure is highly dependent on the action of penicillin-binding proteins (PBPs). While the β-lactam antibiotics have been employed as an antimicrobial strategy for nearly a century, much remains unclear about how inhibitor structure informs potency and PBP isoform selectivity. Here, we obtained high-resolution structures (<2Å) of PBP1b cocrystallized with 6 β-lactams. Surprisingly, 2 structures feature a noncanonical conformation of the covalent "acyl-enzyme complex." To clarify how protein-ligand interactions mediate inhibitor binding, we applied molecular modeling and molecular mechanics-based dynamics analyses. Our analyses illustrate how seemingly minimal changes to inhibitor structure modulate β-lactam binding mode and inhibitor potency, as described by the metric /. Furthermore, we demonstrate that persistent interaction in the covalent acyl-enzyme complex between the inhibitor carboxylate and a highly conserved three-residue motif is not fully predictive of / for PBP1b. modeling suggests that the noncovalent preacyl complex may leverage this interaction, but a postacylation change in ligand conformation may accompany acylation in some inhibitors. The elucidation of key PBP1b ligand-receptor interactions pre- and postacylation will inform the rational design of novel PBP inhibitors and probes.

PubMed: 41589753
DOI: 10.1021/acschembio.5c00788

実験手法

X-RAY DIFFRACTION (1.792 Å)