ArticleBiochemistry2010
Structural characterization of the Mycobacterium tuberculosis biotin biosynthesis enzymes 7,8-diaminopelargonic acid synthase and dethiobiotin synthetase .
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 61 citations in OpenAlex.
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- 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
- Toad's survivability and soil microbiome alterations impacted via individual abundance.Biologia futura · 2025Article
- A split ALFA tag-nanobody system for protein localization and proximity proteomics in mycobacteria.mBio · 2025Article
- Live Attenuated Vaccines against Tuberculosis: Targeting the Disruption of Genes Encoding the Secretory Proteins of Mycobacteria.Vaccines · 2024Review
- Gallein and isoniazid act synergistically to attenuatebioRxiv : the preprint server for biology · 2024Article
- Gallein potentiates isoniazid's ability to suppressFrontiers in microbiology · 2024Article
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- Antitubercular, Cytotoxicity, and Computational Target Validation of Dihydroquinazolinone Derivatives.Antibiotics (Basel, Switzerland) · 2022Article
- "Upcycling" known molecules and targets for drug-resistant TB.Frontiers in cellular and infection microbiology · 2022Article
- Insights into the molecular determinants involved inVirulence · 2021Review
- The Multifaceted Bacterial Cysteine Desulfurases: From Metabolism to Pathogenesis.Antioxidants (Basel, Switzerland) · 2021Review
- Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets.Frontiers in cellular and infection microbiology · 2021Review
- 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
- Structural dynamics of the transaminase active site revealed by the crystal structure of a co-factor free omega-transaminase from Vibrio fluvialis JS17.Scientific reports · 2018Article
- Identification ofDrug design, development and therapy · 2018Article
- Identification of a novel class of small compounds with anti-tuberculosis activity by in silico structure-based drug screening.The Journal of antibiotics · 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
- bioA mutant of Mycobacterium tuberculosis shows severe growth defect and imparts protection against tuberculosis in guinea pigs.PloS one · 2017Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Mycobacterium tuberculosis (Mtb) depends on biotin synthesis for survival during infection. In the absence of biotin, disruption of the biotin biosynthesis pathway results in cell death rather than growth arrest, an unusual phenotype for an Mtb auxotroph. Humans lack the enzymes for biotin production, making the proteins of this essential Mtb pathway promising drug targets. To this end, we have determined the crystal structures of the second and third enzymes of the Mtb biotin biosynthetic pathway, 7,8-diaminopelargonic acid synthase (DAPAS) and dethiobiotin synthetase (DTBS), at respective resolutions of 2.2 and 1.85 A. Superimposition of the DAPAS structures bound either to the SAM analogue sinefungin or to 7-keto-8-aminopelargonic acid (KAPA) allowed us to map the putative binding site for the substrates and to propose a mechanism by which the enzyme accommodates their disparate structures. Comparison of the DTBS structures bound to the substrate 7,8-diaminopelargonic acid (DAPA) or to ADP and the product dethiobiotin (DTB) permitted derivation of an enzyme mechanism. There are significant differences between the Mtb enzymes and those of other organisms; the Bacillus subtilis DAPAS, presented here at a high resolution of 2.2 A, has active site variations and the Escherichia coli and Helicobacter pylori DTBS have alterations in their overall folds. We have begun to exploit the unique characteristics of the Mtb structures to design specific inhibitors against the biotin biosynthesis pathway in Mtb.
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