9KBT
Crystal structure of PHAB8, a peptidoglycan hydrolase with relatively weak thermal stability and broad-spectrum.
Summary for 9KBT
| Entry DOI | 10.2210/pdb9kbt/pdb |
| Descriptor | Lysozyme, GLYCEROL, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | peptidoglycan dydrolase, cationic peptides, monomer, lyase |
| Biological source | Acinetobacter baumannii |
| Total number of polymer chains | 1 |
| Total formula weight | 22998.00 |
| Authors | |
| Primary citation | 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 Cited by 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: 39589395DOI: 10.7554/eLife.98266 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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