9PME

Crystallographic structure of MazF-E24A toxin bound to SamF

Summary for 9PME

• Entry DOI: 10.2210/pdb9pme/pdb
• Descriptor: Endoribonuclease toxin MazF, peptide SER-HIS-LEU-PHE-TRP-ALA-GLN-PHE-ASP-GLU-TYR-PHE, SODIUM ION, ... (4 entities in total)
• Functional Keywords: mazf, toxin-antitoxin system, mazf inhibitor, toxin
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 2
• Total formula weight: 13691.73

Authors

Pizzolato-Cezar, L.R.,Nascimento, A.F.Z.,Machini, M.T.,Salinas, R.K. (deposition date: 2025-07-17, release date: 2025-10-29)

Primary citation

Pizzolato-Cezar, L.R.,Vitale, P.M.,Liria, C.W.,Pineda, M.A.R.,Lacerda, C.D.,Marana, S.R.,Nascimento, A.F.Z.,Sassonia, R.C.,Sgro, G.G.,Salinas, R.K.,Machini, M.T.
Development of a Potent and Functional In Vivo Peptide Competitive Inhibitor for the Toxin MazF.
J.Med.Chem., 2025

PubMed Abstract: Cell growth regulation granted by toxin-antitoxin systems enables bacteria to fight phage infections, evade host immune defenses, and survive antibiotic treatment. In this work, a potent and specific peptide competitive inhibitor for the toxin MazF was developed and named Small Antitoxin of MazF (SamF). Employing a set of -acetylated and -amidated synthetic peptides, biophysical methods, biochemistry, and molecular biology techniques, we demonstrated that SamF binds tightly and with high specificity to MazF and , blocking access to the substrate binding site. Coexpression of SamF with MazF in efficiently counteracted the metabolic downregulation imposed by the toxin and the formation of antibiotic persisters. Altogether, our data uncovered a new MazF druggable site and an excellent scaffold for the design of antimicrobials. SamF is also a promising tool to study MazF and its physiological function in bacteria.

PubMed: 41081386
DOI: 10.1021/acs.jmedchem.5c02001

Experimental method

X-RAY DIFFRACTION (1.52 Å)