ArticleProtein science : a publication of the Protein Society2020
Allosteric inhibitors of Mycobacterium tuberculosis tryptophan synthase.
Article in Protein science : a publication of the Protein Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- The Pyridoxal-5'-Phosphate-Dependent Enzymes ofACS infectious diseases · 2026Review
- Tryptophan production by catalysis of a putative tryptophan synthase protein.Archives of microbiology · 2024Article
- 5-Fluoroindole Reduces the Bacterial Burden in a Murine Model ofACS omega · 2024Article
- Neutron diffraction from a microgravity-grown crystal reveals the active site hydrogens of the internal aldimine form of tryptophan synthase.Cell reports. Physical science · 2024Article
- Fungi Tryptophan Synthases: What Is the Role of the Linker Connecting the α and β Structural Domains inMolecules (Basel, Switzerland) · 2024Article
- Analytical methods for stable isotope labeling to elucidate rapid auxin kinetics in Arabidopsis thaliana.PloS one · 2024Article
- Investigating the Roles of Active Site Residues inACS bio & med chem Au · 2023Article
- Review
- Computational Analysis on the Allostery of Tryptophan Synthase: Relationship between α/β-Ligand Binding and Distal Domain Closure.The journal of physical chemistry. B · 2022Article
- Discovery of antimicrobial agent targeting tryptophan synthase.Protein science : a publication of the Protein Society · 2022Article
- Atomic-resolution chemical characterization of (2x)72-kDa tryptophan synthase via four- and five-dimensionalProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Indole-3-Glycerol Phosphate Synthase From Mycobacterium tuberculosis: A Potential New Drug Target.Chembiochem : a European journal of chemical biology · 2022Review
- Indole: A promising scaffold for the discovery and development of potential anti-tubercular agents.Current research in pharmacology and drug discovery · 2022Review
- An Outline of the Latest Crystallographic Studies on Inhibitor-Enzyme Complexes for the Design and Development of New Therapeutics against Tuberculosis.Molecules (Basel, Switzerland) · 2021Review
- Resistance of Mycobacterium tuberculosis to indole 4-carboxamides occurs through alterations in drug metabolism and tryptophan biosynthesis.Cell chemical biology · 2021Article
- Protocol: analytical methods for visualizing the indolic precursor network leading to auxin biosynthesis.Plant methods · 2021Article
- Distinct conformational dynamics and allosteric networks in alpha tryptophan synthase during active catalysis.Protein science : a publication of the Protein Society · 2021Article
- Design, Synthesis, and Biological Evaluation of a Series of 5- and 7-Hydroxycoumarin Derivatives as 5-HTPharmaceuticals (Basel, Switzerland) · 2021Article
- The tryptophan biosynthetic pathway is essential for Mycobacterium tuberculosis to cause disease.Biochemical Society transactions · 2020Review
- Regio- and Diastereoselective Synthesis of 2-Arylazetidines: Quantum Chemical Explanation of Baldwin's Rules for the Ring-Formation Reactions of Oxiranes†.The Journal of organic chemistry · 2020Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Global dispersion of multidrug resistant bacteria is very common and evolution of antibiotic-resistance is occurring at an alarming rate, presenting a formidable challenge for humanity. The development of new therapeuthics with novel molecular targets is urgently needed. Current drugs primarily affect protein, nucleic acid, and cell wall synthesis. Metabolic pathways, including those involved in amino acid biosynthesis, have recently sparked interest in the drug discovery community as potential reservoirs of such novel targets. Tryptophan biosynthesis, utilized by bacteria but absent in humans, represents one of the currently studied processes with a therapeutic focus. It has been shown that tryptophan synthase (TrpAB) is required for survival of Mycobacterium tuberculosis in macrophages and for evading host defense, and therefore is a promising drug target. Here we present crystal structures of TrpAB with two allosteric inhibitors of M. tuberculosis tryptophan synthase that belong to sulfolane and indole-5-sulfonamide chemical scaffolds. We compare our results with previously reported structural and biochemical studies of another, azetidine-containing M. tuberculosis tryptophan synthase inhibitor. This work shows how structurally distinct ligands can occupy the same allosteric site and make specific interactions. It also highlights the potential benefit of targeting more variable allosteric sites of important metabolic enzymes.
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