9KBS

Crystal structure of PHAb11, another peptidoglycan hydrolase with thermal stability and broad-spectrum

9KBS の概要

• エントリーDOI: 10.2210/pdb9kbs/pdb
• 分子名称: Lysozyme, GLYCEROL (3 entities in total)
• 機能のキーワード: peptidoglycan dydrolase, cationic peptides, dimer, lyase
• 由来する生物種: Acinetobacter baumannii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40111.94

構造登録者

Hu, F. (登録日: 2024-10-31, 公開日: 2024-11-27, 最終更新日: 2025-06-18)

主引用文献

Zhang, L.,Hu, F.,Zhao, Z.,Li, X.,Zhong, M.,He, J.,Yao, F.,Zhang, X.,Mao, Y.,Wei, H.,He, J.,Yang, H.
Dimer-monomer transition defines a hyper-thermostable peptidoglycan hydrolase mined from bacterial proteome by lysin-derived antimicrobial peptide-primed screening.
Elife, 13:-, 2024

PubMed Abstract: Phage-derived peptidoglycan hydrolases (i.e. lysins) are considered promising alternatives to conventional antibiotics due to their direct peptidoglycan degradation activity and low risk of resistance development. The discovery of these enzymes is often hampered by the limited availability of phage genomes. Herein, we report a new strategy to mine active peptidoglycan hydrolases from bacterial proteomes by lysin-derived antimicrobial peptide-primed screening. As a proof-of-concept, five eptidoglycan ydrolases from the proteome (PHAb7-PHAb11) were identified using PlyF307 lysin-derived peptide as a template. Among them, PHAb10 and PHAb11 showed potent bactericidal activity against multiple pathogens even after treatment at 100°C for 1 hr, while the other three were thermosensitive. We solved the crystal structures of PHAb8, PHAb10, and PHAb11 and unveiled that hyper-thermostable PHAb10 underwent a unique folding-refolding thermodynamic scheme mediated by a dimer-monomer transition, while thermosensitive PHAb8 formed a monomer. Two mouse models of bacterial infection further demonstrated the safety and efficacy of PHAb10. In conclusion, our antimicrobial peptide-primed strategy provides new clues for the discovery of promising antimicrobial drugs.

PubMed: 39589395
DOI: 10.7554/eLife.98266

実験手法

X-RAY DIFFRACTION (2.27 Å)