ArticleCommunications biology2022
Structure-guided functional studies of plasmid-encoded dihydrofolate reductases reveal a common mechanism of trimethoprim resistance in Gram-negative pathogens.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Mutation analysis of dihydrofolate reductase (Iranian journal of microbiology · 2026Article
- Annotating the pangenome reveals the diversity in the genetic basis for metabolic enzymes.Science advances · 2026Article
- Engineering Protein Stability with Small Molecules: A Review of the ecDHFR Destabilizing Domain System.ACS chemical biology · 2026Review
- Chaperonin recognition of protein dynamics drives drug resistance.bioRxiv : the preprint server for biology · 2026Article
- Article
- GCMS-based evaluation, characterization and in silico analysis of antimicrobial metabolites in the crude extract of cold-adaptedAIMS microbiology · 2026Article
- A bright and regenerative array tag with fluorogenic ligands for long-term live-cell nanoscopy and single-molecule tracking.Nature communications · 2025Article
- Comprehensive Genomic and Phenotypic Characterization ofMicroorganisms · 2025Article
- Exploring antibiotic resistance in diverse homologs of the dihydrofolate reductase protein family through broad mutational scanning.Science advances · 2025Article
- Trimethoprim resistance inJournal of medical microbiology · 2025Article
- Expanding the Landscape of Dual Action Antifolate Antibacterials through 2,4-Diamino-1,6-dihydro-1,3,5-triazines.ACS infectious diseases · 2025Article
- High throughput screening identifies potential inhibitors targeting trimethoprim resistant DfrA1 protein in Klebsiella pneumoniae and Escherichia coli.Scientific reports · 2025Article
- Article
- Studies Regarding Antimicrobial Properties of Some Microbial Polyketides Derived fromAntibiotics (Basel, Switzerland) · 2024Article
- Article
- Clinical Setting Comparative Analysis of Uropathogens and Antibiotic Resistance: A Retrospective Study Spanning the Coronavirus Disease 2019 Pandemic.Open forum infectious diseases · 2024Article
- Protein-Ligand Blind Docking Using CB-Dock2.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Molecular Marvels: Small Molecules Paving the Way for Enhanced Gene Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Unveiling the Efficacy of Sesquiterpenes from Marine SpongeMolecules (Basel, Switzerland) · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Two plasmid-encoded dihydrofolate reductase (DHFR) isoforms, DfrA1 and DfrA5, that give rise to high levels of resistance in Gram-negative bacteria were structurally and biochemically characterized to reveal the mechanism of TMP resistance and to support phylogenic groupings for drug development against antibiotic resistant pathogens. Preliminary screening of novel antifolates revealed related chemotypes that showed high levels of inhibitory potency against Escherichia coli chromosomal DHFR (EcDHFR), DfrA1, and DfrA5. Kinetics and biophysical analysis, coupled with crystal structures of trimethoprim bound to EcDHFR, DfrA1 and DfrA5, and two propargyl-linked antifolates (PLA) complexed with EcDHFR, DfrA1 and DfrA5, were determined to define structural features of the substrate binding pocket and guide synthesis of pan-DHFR inhibitors.
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