ArticleBiochimica et biophysica acta2016
Visualizing the tunnel in tryptophan synthase with crystallography: Insights into a selective filter for accommodating indole and rejecting water.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed.
- Molecular Mechanisms of Interaction of Human Serum Albumin with the CD36 Receptor: Insights from Molecular Dynamics Simulations.International journal of molecular sciences · 2026Article
- Crystallographic fragment-binding studies of the Mycobacterium tuberculosis trifunctional enzyme suggest binding pockets for the tails of the acyl-CoA substrates at its active sites and a potential substrate-channeling path between them.Acta crystallographica. Section D, Structural biology · 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
- Discovery of antimicrobial agent targeting tryptophan synthase.Protein science : a publication of the Protein Society · 2022Article
- Imaging active site chemistry and protonation states: NMR crystallography of the tryptophan synthase α-aminoacrylate intermediate.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Allosteric regulation of substrate channeling:Frontiers in molecular biosciences · 2022Review
- Mutation of βGln114 to Ala Alters the Stabilities of Allosteric States in Tryptophan Synthase Catalysis.Biochemistry · 2021Article
- Catalytically impaired TrpA subunit of tryptophan synthase from Chlamydia trachomatis is an allosteric regulator of TrpB.Protein science : a publication of the Protein Society · 2021Article
- Resistance of Mycobacterium tuberculosis to indole 4-carboxamides occurs through alterations in drug metabolism and tryptophan biosynthesis.Cell chemical biology · 2021Article
- Self-Organization and Information Processing: From Basic Enzymatic Activities to Complex Adaptive Cellular Behavior.Frontiers in genetics · 2021Review
- Backbone assignments and conformational dynamics in the S. typhimurium tryptophan synthase α-subunit from solution-state NMR.Journal of biomolecular NMR · 2020Article
- Co-localization and confinement of ecto-nucleotidases modulate extracellular adenosine nucleotide distributions.PLoS computational biology · 2020Article
- Allosteric inhibitors of Mycobacterium tuberculosis tryptophan synthase.Protein science : a publication of the Protein Society · 2020Article
- Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway.Nature communications · 2019Article
- Direct dynamic nuclear polarization ofSolid state nuclear magnetic resonance · 2019Article
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- A small-molecule allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase.Nature chemical biology · 2017Article
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8 authors.
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Abstract
Four new X-ray structures of tryptophan synthase (TS) crystallized with varying numbers of the amphipathic N-(4'-trifluoromethoxybenzoyl)-2-aminoethyl phosphate (F6) molecule are presented. These structures show one of the F6 ligands threaded into the tunnel from the β-site and reveal a distinct hydrophobic region. Over this expanse, the interactions between F6 and the tunnel are primarily nonpolar, while the F6 phosphoryl group fits into a polar pocket of the β-subunit active site. Further examination of TS structures reveals that one portion of the tunnel (T1) binds clusters of water molecules, whereas waters are not observed in the nonpolar F6 binding region of the tunnel (T2). MD simulation of another TS structure with an unobstructed tunnel also indicates the T2 region of the tunnel excludes water, consistent with a dewetted state that presents a significant barrier to the transfer of water into the closed β-site. We conclude that hydrophobic molecules can freely diffuse between the α- and β-sites via the tunnel, while water does not. We propose that exclusion of water serves to inhibit reaction of water with the α-aminoacrylate intermediate to form ammonium ion and pyruvate, a deleterious side reaction in the αβ-catalytic cycle. Finally, while most TS structures show βPhe280 partially blocking the tunnel between the α- and β-sites, new structures show an open tunnel, suggesting the flexibility of the βPhe280 side chain. Flexible docking studies and MD simulations confirm that the dynamic behavior of βPhe280 allows unhindered transfer of indole through the tunnel, therefore excluding a gating role for this residue.
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