ArticleJournal of the American Chemical Society2011
Mechanism-based inactivation by aromatization of the transaminase BioA involved in biotin biosynthesis in Mycobaterium tuberculosis.
Article in Journal of the American Chemical Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Induced alanine auxotrophy as a therapeutic strategy against Mycobacterium tuberculosis.Research square · 2026Article
- Integrating chemical, genetic, and feasibility assessments for anti-tubercular target validation.EMBO molecular medicine · 2026Review
- 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
- Three enigmatic BioH isoenzymes are programmed in the early stage of mycobacterial biotin synthesis, an attractive anti-TB drug target.PLoS pathogens · 2022Article
- The primary step of biotin synthesis in mycobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Biotin Biosynthetic Pathway in Mycobacterium tuberculosis is a Validated Target for the Development of Antibacterial Agents.Current medicinal chemistry · 2020Review
- Combined In Vitro Studies and in Silico Target Fishing for the Evaluation of the Biological Activities ofMolecules (Basel, Switzerland) · 2018Article
- Targeting protein biotinylation enhances tuberculosis chemotherapy.Science translational medicine · 2018Article
- Identification ofDrug design, development and therapy · 2018Article
- Control of biotin biosynthesis in mycobacteria by a pyruvate carboxylase dependent metabolic signal.Molecular microbiology · 2017Article
- Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1'-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators.Journal of the American Chemical Society · 2017Article
- Synthesis of a 3-Amino-2,3-dihydropyrid-4-one and Related Heterocyclic Analogues as Mechanism-Based Inhibitors of BioA, a Pyridoxal Phosphate-Dependent Enzyme.The Journal of organic 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
- Rational Optimization of Mechanism-Based Inhibitors through Determination of the Microscopic Rate Constants of Inactivation.Journal of the American Chemical Society · 2017Article
- In silico discovery and in vitro activity of inhibitors againstDrug design, development and therapy · 2017Article
- Fragment-based exploration of binding site flexibility in Mycobacterium tuberculosis BioA.Journal of medicinal chemistry · 2015Article
- Genetic Approaches to Facilitate Antibacterial Drug Development.Cold Spring Harbor perspectives in medicine · 2015Review
- Target-based identification of whole-cell active inhibitors of biotin biosynthesis in Mycobacterium tuberculosis.Chemistry & biology · 2015Article
- The application of tetracyclineregulated gene expression systems in the validation of novel drug targets in Mycobacterium tuberculosis.Frontiers in microbiology · 2015Review
- Mycobacterium tuberculosis metabolism.Cold Spring Harbor perspectives in medicine · 2014Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
BioA catalyzes the second step of biotin biosynthesis, and this enzyme represents a potential target to develop new antitubercular agents. Herein we report the design, synthesis, and biochemical characterization of a mechanism-based inhibitor (1) featuring a 3,6-dihydropyrid-2-one heterocycle that covalently modifies the pyridoxal 5'-phosphate (PLP) cofactor of BioA through aromatization. The structure of the PLP adduct was confirmed by MS/MS and X-ray crystallography at 1.94 Å resolution. Inactivation of BioA by 1 was time- and concentration-dependent and protected by substrate. We used a conditional knock-down mutant of M. tuberculosis to demonstrate the antitubercular activity of 1 correlated with BioA expression, and these results provide support for the designed mechanism of action.
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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.