ArticleJournal of medicinal chemistry2015
Fragment-based exploration of binding site flexibility in Mycobacterium tuberculosis BioA.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Structure-Guided Development of a Potent BioA Inhibitor Validates Biotin Synthesis Inhibition as a Therapeutic Strategy for Tuberculosis.bioRxiv : the preprint server for biology · 2025Article
- Unlocking GPCR-ligand interactions: Measuring binding affinities with thermal shift assay.Protein science : a publication of the Protein Society · 2025Article
- ShiftScan: A tool for rapid analysis of high-throughput differential scanning fluorimetry data and compound prioritization.Protein science : a publication of the Protein Society · 2025Article
- Thermal shift assay to identify ligands for bacterial sensor proteins.FEMS microbiology reviews · 2025Review
- Target-based drug discovery: Applications of fluorescence techniques in high throughput and fragment-based screening.Heliyon · 2024Review
- Thermal unfolding methods in drug discovery.Biophysics reviews · 2023Review
- The opportunistic pathogen Pseudomonas aeruginosa exploits bacterial biotin synthesis pathway to benefit its infectivity.PLoS pathogens · 2023Article
- Three enigmatic BioH isoenzymes are programmed in the early stage of mycobacterial biotin synthesis, an attractive anti-TB drug target.PLoS pathogens · 2022Article
- Antitubercular, Cytotoxicity, and Computational Target Validation of Dihydroquinazolinone Derivatives.Antibiotics (Basel, Switzerland) · 2022Article
- Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy.Science (New York, N.Y.) · 2022Article
- A missense mutation in a patient with developmental delay affects the activity and structure of the hexosamine biosynthetic pathway enzyme AGX1.FEBS letters · 2021Article
- Theory and applications of differential scanning fluorimetry in early-stage drug discovery.Biophysical reviews · 2020Review
- The Biotin Biosynthetic Pathway in Mycobacterium tuberculosis is a Validated Target for the Development of Antibacterial Agents.Current medicinal chemistry · 2020Review
- Isothermal Analysis of ThermoFluor Data can readily provide Quantitative Binding Affinities.Scientific reports · 2019Article
- Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach.ACS chemical biology · 2018Article
- Identification ofDrug design, development and therapy · 2018Article
- Mind the Metal: A Fragment Library-Derived Zinc Impurity Binds the E2 Ubiquitin-Conjugating Enzyme Ube2T and Induces Structural Rearrangements.Journal of medicinal chemistry · 2017Article
- Structure-Based Optimization of Pyridoxal 5'-Phosphate-Dependent Transaminase Enzyme (BioA) Inhibitors that Target Biotin Biosynthesis in Mycobacterium tuberculosis.Journal of medicinal chemistry · 2017Article
- Optimal allosteric stabilization sites using contact stabilization analysis.Journal of computational chemistry · 2017Article
- Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening.Journal of medicinal chemistry · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The PLP-dependent transaminase (BioA) of Mycobacterium tuberculosis and other pathogens that catalyzes the second step of biotin biosynthesis is a now well-validated target for antibacterial development. Fragment screening by differential scanning fluorimetry has been performed to discover new chemical scaffolds and promote optimization of existing inhibitors. Calorimetry confirms binding of six molecules with high ligand efficiency. Thermodynamic data identifies which molecules bind with the enthalpy driven stabilization preferred in compounds that represent attractive starting points for future optimization. Crystallographic characterization of complexes with these molecules reveals the dynamic nature of the BioA active site. Different side chain conformational states are stabilized in response to binding by different molecules. A detailed analysis of conformational diversity in available BioA structures is presented, resulting in the identification of two states that might be targeted with molecular scaffolds incorporating well-defined conformational attributes. This new structural data can be used as part of a scaffold hopping strategy to further optimize existing inhibitors or create new small molecules with improved therapeutic potential.
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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.