ArticleProceedings of the National Academy of Sciences of the United States of America2022
Imaging active site chemistry and protonation states: NMR crystallography of the tryptophan synthase α-aminoacrylate intermediate.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed.
- NMR crystallography reveals active-site protonation states of Toho-1 β-lactamase in complex with avibactam.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Speciation, Structural Refinement, and Distribution of Ti Sites in Titanium Silicalite-1 FromAngewandte Chemie (International ed. in English) · 2026Article
- Rapid Assignment of Chemical Shifts From Crystal Structures in Solid-State NMR.Angewandte Chemie (International ed. in English) · 2026Article
- Pyridoxal 5'-Phosphate-Dependent Enzymatic Decarboxylative Annulation.Journal of the American Chemical Society · 2026Article
- Revealing structure and shaping priorities in plant and fungal cell wall architecture via solid-state NMR.Cell surface (Amsterdam, Netherlands) · 2025Review
- MAS Cryoprobe Enhances Solid-State NMR Signals of α-Synuclein Fibrils.bioRxiv : the preprint server for biology · 2025Article
- Determination of key functional structures of an amorphous VHL-based SMARCA2 PROTAC.Nature communications · 2025Article
- α-Hydrazino Acids Inhibit Pyridoxal Phosphate-Dependent Decarboxylases via "Catalytically Correct" Ketoenamine Tautomers: A Special Motif for Chemical Biology and Drug Discovery?ACS catalysis · 2025Article
- Uniform chi-squared model probabilities in NMR crystallography.Faraday discussions · 2025Article
- Spiers Memorial Lecture: NMR crystallography.Faraday discussions · 2025Article
- The interplay of density functional selection and crystal structure for accurate NMR chemical shift predictions.Faraday discussions · 2025Article
- Dipolar Recoupling in Rotating Solids.Chemical reviews · 2024Review
- Sedimentation of large, soluble proteins up to 140 kDa forJournal of biomolecular NMR · 2024Article
- Elucidation of the stereochemical mechanism of cystathionine γ-lyase reveals how substrate specificity constrains catalysis.ACS catalysis · 2024Article
- Resolution in cryogenic solid state NMR: Challenges and solutions.Protein science : a publication of the Protein Society · 2024Review
- Article
- Solid-state NMR MAS CryoProbe enables structural studies of human blood protein vitronectin bound to hydroxyapatite.Journal of structural biology · 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
- Molecular mechanisms and evolutionary robustness of a color switch in proteorhodopsins.Science advances · 2024Article
- Engineered Biocatalytic Synthesis of β-N-Substituted-α-Amino Acids.Angewandte Chemie (International ed. in English) · 2023Article
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25 authors.
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Abstract
NMR-assisted crystallography-the integrated application of solid-state NMR, X-ray crystallography, and first-principles computational chemistry-holds significant promise for mechanistic enzymology: by providing atomic-resolution characterization of stable intermediates in enzyme active sites, including hydrogen atom locations and tautomeric equilibria, NMR crystallography offers insight into both structure and chemical dynamics. Here, this integrated approach is used to characterize the tryptophan synthase α-aminoacrylate intermediate, a defining species for pyridoxal-5'-phosphate-dependent enzymes that catalyze β-elimination and replacement reactions. For this intermediate, NMR-assisted crystallography is able to identify the protonation states of the ionizable sites on the cofactor, substrate, and catalytic side chains as well as the location and orientation of crystallographic waters within the active site. Most notable is the water molecule immediately adjacent to the substrate β-carbon, which serves as a hydrogen bond donor to the ε-amino group of the acid-base catalytic residue βLys87. From this analysis, a detailed three-dimensional picture of structure and reactivity emerges, highlighting the fate of the L-serine hydroxyl leaving group and the reaction pathway back to the preceding transition state. Reaction of the α-aminoacrylate intermediate with benzimidazole, an isostere of the natural substrate indole, shows benzimidazole bound in the active site and poised for, but unable to initiate, the subsequent bond formation step. When modeled into the benzimidazole position, indole is positioned with C3 in contact with the α-aminoacrylate C
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