ArticleACS chemical biology2017
Structural Flexibility of an Inhibitor Overcomes Drug Resistance Mutations in Staphylococcus aureus FtsZ.
Article in ACS chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 67 citations in OpenAlex.
- Computationally Generated Plant-Derived Berberine-Based Hybrid Compounds as Potential Dual Binders toInternational journal of molecular sciences · 2026Article
- Antibacterial drug discovery: challenges and preclinical promises from synthetic small molecules.Chemical Society reviews · 2026Review
- Development of Broad-Spectrum Antimicrobial Peptides through the Conjugation of FtsZ-Binding and Cell-Penetrating Peptides.ACS infectious diseases · 2025Article
- FtsZ as a novel target for antibiotics development: Promises and challenges.Acta pharmaceutica Sinica. B · 2025Review
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
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- Compounds fromFrontiers in microbiology · 2025Article
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- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Computational docking of FtsZ: Survey of promising antibiotic compounds.Biochemistry and biophysics reports · 2024Article
- Molecular dynamics simulations reveal differences in the conformational stability of FtsZs derived from Staphylococcus aureus and Bacillus subtilis.Scientific reports · 2024Article
- A FtsZ Inhibitor That Can Utilize Siderophore-Ferric Iron Uptake Transporter Systems for Activity against Gram-Negative Bacterial Pathogens.Antibiotics (Basel, Switzerland) · 2024Article
- Benzodioxane-Benzamides as FtsZ Inhibitors: Effects of Linker's Functionalization on Gram-Positive Antimicrobial Activity.Antibiotics (Basel, Switzerland) · 2023Article
- Unrealized targets in the discovery of antibiotics for Gram-negative bacterial infections.Nature reviews. Drug discovery · 2023Review
- Novel antimicrobial strategies to treat multi-drug resistant Staphylococcus aureus infections.Microbial biotechnology · 2023Review
- Filamentous temperature sensitive mutant Z: a putative target to combat antibacterial resistance.RSC advances · 2023Review
- Structural and Antibacterial Characterization of a New Benzamide FtsZ Inhibitor with Superior Bactericidal Activity and In Vivo Efficacy Against Multidrug-ResistantACS chemical biology · 2023Article
- A mechanism of salt bridge-mediated resistance to FtsZ inhibitor PC190723 revealed by a cell-based screen.Molecular biology of the cell · 2023Article
- Models versus pathogens: how conserved is the FtsZ in bacteria?Bioscience reports · 2023Review
- Synthesis and In Vitro Antimicrobial SAR of Benzyl and Phenyl Guanidine and Aminoguanidine Hydrazone Derivatives.Molecules (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
In the effort to combat antibiotic resistance, inhibitors of the essential bacterial protein FtsZ have emerged as a promising new class of compounds with clinical potential. One such FtsZ inhibitor (TXA707) is associated with potent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) that are resistant to current standard-of-care antibiotics. However, mutations in S. aureus FtsZ (SaFtsZ) that confer resistance to TXA707 have been observed, with mutations in the Gly196 and Gly193 residues being among the most prevalent. Here, we describe structural studies of an FtsZ inhibitor, TXA6101, which retains activity against MRSA isolates that express either G196S or G193D mutant FtsZ. We present the crystal structures of TXA6101 in complex with both wild-type SaFtsZ and G196S mutant SaFtsZ, as well the crystal structure of TXA707 in complex with wild-type SaFtsZ. Comparison of the three structures reveals a molecular basis for the differential targeting abilities of TXA6101 and TXA707. The greater structural flexibility of TXA6101 relative to TXA707 enables TXA6101 to avoid steric clashes with Ser196 and Asp193. Our structures also demonstrate that the binding of TXA6101 induces previously unobserved conformational rearrangements of SaFtsZ residues in the binding pocket. In aggregate, the structures reported in this work reveal key factors for overcoming drug resistance mutations in SaFtsZ and offer a structural basis for the design of FtsZ inhibitors with enhanced antibacterial potency and reduced susceptibility to mutational resistance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.