ArticleChemistry & biology2011
Bisubstrate adenylation inhibitors of biotin protein ligase from Mycobacterium tuberculosis.
Article in Chemistry & biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 89 citations in OpenAlex.
- Synthesis of New DltA Inhibitors and Their Application as Adjuvant Antibiotics to Re-Sensitize Methicillin-ResistantMolecules (Basel, Switzerland) · 2025Article
- Co-crystal structure of Helicobacter pylori biotin protein ligase with biotinyl-5-ATP.Acta crystallographica. Section F, Structural biology communications · 2025Article
- New Potent Sulfonamide-Based Inhibitors ofACS medicinal chemistry letters · 2024Article
- The implication of Mycobacterium tuberculosis-mediated metabolism of targeted xenobiotics.Nature reviews. Chemistry · 2023Review
- Structural Study of Potent Triazole-Based Inhibitors ofACS medicinal chemistry letters · 2023Article
- The opportunistic pathogen Pseudomonas aeruginosa exploits bacterial biotin synthesis pathway to benefit its infectivity.PLoS pathogens · 2023Article
- Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance.Nature communications · 2022Article
- Spatiotemporal Proximity Labeling Tools to Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling.ACS chemical biology · 2022Article
- Three enigmatic BioH isoenzymes are programmed in the early stage of mycobacterial biotin synthesis, an attractive anti-TB drug target.PLoS pathogens · 2022Article
- Development of small-molecule inhibitors of fatty acyl-AMP and fatty acyl-CoA ligases in Mycobacterium tuberculosis.European journal of medicinal chemistry · 2020Article
- Advanced Resistance Studies Identify Two Discrete Mechanisms inAntibiotics (Basel, Switzerland) · 2020Article
- Gram-scale preparation of the antibiotic lead compound salicyl-AMS, a potent inhibitor of bacterial salicylate adenylation enzymes.Methods in enzymology · 2020Article
- The Biotin Biosynthetic Pathway in Mycobacterium tuberculosis is a Validated Target for the Development of Antibacterial Agents.Current medicinal chemistry · 2020Review
- A Novel Lipoate-Protein Ligase, Mhp-LplJ, Is Required for Lipoic Acid Metabolism inFrontiers in microbiology · 2020Article
- Hybrid Dynamic Pharmacophore Models as Effective Tools to Identify Novel Chemotypes for Anti-TB Inhibitor Design: A Case Study With Mtb-DapB.Frontiers in chemistry · 2020Article
- Functional Identification and Structural Analysis of a New Lipoate Protein Ligase inFrontiers in cellular and infection microbiology · 2020Article
- Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors.The Journal of antibiotics · 2019Review
- Investigation of ( S)-(-)-Acidomycin: A Selective Antimycobacterial Natural Product That Inhibits Biotin Synthase.ACS infectious diseases · 2019Article
- Genome-wide discovery of epistatic loci affecting antibiotic resistance in Neisseria gonorrhoeae using evolutionary couplings.Nature microbiology · 2019Article
- Avoiding Antibiotic Inactivation in Mycobacterium tuberculosis by Rv3406 through Strategic Nucleoside Modification.ACS infectious diseases · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The mycobacterial biotin protein ligase (MtBPL) globally regulates lipid metabolism in Mtb through the posttranslational biotinylation of acyl coenzyme A carboxylases involved in lipid biosynthesis that catalyze the first step in fatty acid biosynthesis and pyruvate coenzyme A carboxylase, a gluconeogenic enzyme vital for lipid catabolism. Here we describe the design, development, and evaluation of a rationally designed bisubstrate inhibitor of MtBPL. This inhibitor displays potent subnanomolar enzyme inhibition and antitubercular activity against multidrug resistant and extensively drug resistant Mtb strains. We show that the inhibitor decreases in vivo protein biotinylation of key enzymes involved in fatty acid biosynthesis and that the antibacterial activity is MtBPL dependent. Additionally, the gene encoding BPL was found to be essential in M. smegmatis. Finally, the X-ray cocrystal structure of inhibitor bound MtBPL was solved providing detailed insight for further structure-activity analysis. Collectively, these data suggest that MtBPL is a promising target for further antitubercular therapeutic development.
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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.