ArticleStructure (London, England : 1993)2012
Structure of Ddn, the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis involved in bioreductive activation of PA-824.
Article in Structure (London, England : 1993), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 108 citations in OpenAlex.
- Article
- Editorial: Vaccines and molecular therapeutics for tuberculosis.Frontiers in immunology · 2026Article
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Insights into anti-tuberculosis drug design on the scaffold of nitroimidazole derivatives using structure-based computer-aided approaches.RSC advances · 2025Article
- Pilot Scale Production of a FBiotechnology journal · 2025Article
- Functions of nitroreductases in mycobacterial physiology and drug susceptibility.Journal of bacteriology · 2025Review
- Flavin and deazaflavin biosynthesis in mycobacteria: relevance to physiology, implications for drug discovery, MR-1 antigenicity, and vaccine development.Frontiers in immunology · 2025Review
- You Win Some, You Lose Some: Modifying the Molecular Periphery of Nitrofuran-Tagged Diazaspirooctane Reshapes Its Antibacterial Activity Profile.International journal of molecular sciences · 2024Article
- Cofactor FHeliyon · 2024Article
- Molecular Periphery Design Allows Control of the New Nitrofurans Antimicrobial Selectivity.Molecules (Basel, Switzerland) · 2024Article
- The Nitrofuran-Warhead-Equipped Spirocyclic Azetidines Show Excellent Activity againstMolecules (Basel, Switzerland) · 2024Article
- Both Nitro Groups Are Essential for High Antitubercular Activity of 3,5-Dinitrobenzylsulfanyl Tetrazoles and 1,3,4-Oxadiazoles through the Deazaflavin-Dependent Nitroreductase Activation Pathway.Journal of medicinal chemistry · 2024Article
- Discovery, Synthesis, and Optimization of 1,2,4-Triazolyl Pyridines TargetingACS infectious diseases · 2023Article
- Discovery and characterization of antimycobacterial nitro-containing compounds with distinct mechanisms of action andAntimicrobial agents and chemotherapy · 2023Article
- SigH stress response mediates killing of Mycobacterium tuberculosis by activating nitronaphthofuran prodrugs via induction of Mrx2 expression.Nucleic acids research · 2023Article
- Advances in Key Drug Target Identification and New Drug Development for Tuberculosis.BioMed research international · 2022Review
- On the diversity of FProteins · 2021Article
- Cofactor F420: an expanded view of its distribution, biosynthesis and roles in bacteria and archaea.FEMS microbiology reviews · 2021Article
- Potency boost of aProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Antitubercular and Antiparasitic 2-Nitroimidazopyrazinones with Improved Potency and Solubility.Journal of medicinal chemistry · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Tuberculosis continues to be a global health threat, making bicyclic nitroimidazoles an important new class of therapeutics. A deazaflavin-dependent nitroreductase (Ddn) from Mycobacterium tuberculosis catalyzes the reduction of nitroimidazoles such as PA-824, resulting in intracellular release of lethal reactive nitrogen species. The N-terminal 30 residues of Ddn are functionally important but are flexible or access multiple conformations, preventing structural characterization of the full-length, enzymatically active enzyme. Several structures were determined of a truncated, inactive Ddn protein core with and without bound F(420) deazaflavin coenzyme as well as of a catalytically competent homolog from Nocardia farcinica. Mutagenesis studies based on these structures identified residues important for binding of F(420) and PA-824. The proposed orientation of the tail of PA-824 toward the N terminus of Ddn is consistent with current structure-activity relationship data.
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What OpenQuestion holds
Registered trials
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.