ArticleThe Biochemical journal2021
The structures of E. coli NfsA bound to the antibiotic nitrofurantoin; to 1,4-benzoquinone and to FMN.
Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 28 citations in OpenAlex.
- Selective Reprogramming of Ribosome Assembly and Translational Control during Bacterial Growth Phase Transitions.ACS omega · 2026Article
- Novel TdsD nitroreductase: characterization of kinetics and substrate specificity.Biotechnology letters · 2025Article
- Phase-Specific Antibiotic Resistance Mechanisms in anbioRxiv : the preprint server for biology · 2025Article
- Evolutionary trajectory of bacterial resistance to antibiotics and antimicrobial peptides inmSystems · 2025Article
- Reactions ofInternational journal of molecular sciences · 2025Article
- Genomic insights into plasmid mediated AMR genes, virulence factors and mobile genetic elements in raw milk Escherichia coli from Gujarat, India.Scientific reports · 2025Article
- Improving nitrofurantoin resistance prediction inAntimicrobial agents and chemotherapy · 2024Article
- The Catalysis Mechanism ofInternational journal of molecular sciences · 2024Article
- 5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens.Molecules (Basel, Switzerland) · 2023Article
- Oxygen-insensitive nitroreductase E. coli NfsA, but not NfsB, is inhibited by fumarate.Proteins · 2023Article
- The Crystal Structure of Engineered Nitroreductase NTR 2.0 and Impact of F70A and F108Y Substitutions on Substrate Specificity.International journal of molecular sciences · 2023Article
- Structure and Dynamics of ThreeInternational journal of molecular sciences · 2023Article
- Single-cell recordings reveal subpopulations that grow and generate resistance at bactericidal concentrations of antibiotics.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The 3D-structure, kinetics and dynamics of the E. coli nitroreductase NfsA with NADPFEBS letters · 2022Article
- Molecular Basis of Interactions between the Antibiotic Nitrofurantoin and Human Serum Albumin: A Mechanism for the Rapid Drug Blood Transportation.International journal of molecular sciences · 2021Article
- Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity.International journal of molecular sciences · 2021Review
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8 authors at 3 institutions in 2 countries.
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Abstract
NfsA is a dimeric flavoprotein that catalyses the reduction in nitroaromatics and quinones by NADPH. This reduction is required for the activity of nitrofuran antibiotics. The crystal structure of free Escherichia coli NfsA and several homologues have been determined previously, but there is no structure of the enzyme with ligands. We present here crystal structures of oxidised E. coli NfsA in the presence of several ligands, including the antibiotic nitrofurantoin. Nitrofurantoin binds with the furan ring, rather than the nitro group that is reduced, near the N5 of the FMN. Molecular dynamics simulations show that this orientation is only favourable in the oxidised enzyme, while potentiometry suggests that little semiquinone is formed in the free protein. This suggests that the reduction occurs by direct hydride transfer from FMNH- to nitrofurantoin bound in the reverse orientation to that in the crystal structure. We present a model of nitrofurantoin bound to reduced NfsA in a viable hydride transfer orientation. The substrate 1,4-benzoquinone and the product hydroquinone are positioned close to the FMN N5 in the respective crystal structures with NfsA, suitable for reaction, but are mobile within the active site. The structure with a second FMN, bound as a ligand, shows that a mobile loop in the free protein forms a phosphate-binding pocket. NfsA is specific for NADPH and a similar conformational change, forming a phosphate-binding pocket, is likely to also occur with the natural cofactor.
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