ArticleProceedings of the National Academy of Sciences of the United States of America2019
Mix-and-inject XFEL crystallography reveals gated conformational dynamics during enzyme catalysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 50 citations in OpenAlex.
- Multistate Enzyme Design Enables Efficient and Stereoselective Multistep Catalysis.bioRxiv : the preprint server for biology · 2026Article
- Drop-on-fixed-target reaction initiation approach for serial and time-resolved crystallography.IUCrJ · 2026Article
- Inferring structure factors of weakly populated excited states in perturbative crystallography experiments.bioRxiv : the preprint server for biology · 2026Article
- Serial femtosecond crystallography data processing at the global science data hub center at KISTI.Scientific reports · 2026Article
- Advances in Crystallography and Cryo-Electron Microscopy for the Study of Membrane Proteins.Advances in experimental medicine and biology · 2026Review
- Real-time capture of domain movements during copper amine oxidase catalysis by mix-and-inject serial crystallography.Nature communications · 2025Article
- Sample delivery methods for protein X-ray crystallography with a special focus on sample consumption.Nature communications · 2025Review
- Combining Reactive Quantum-Mechanical Molecular-Dynamics Simulations with Mutagenesis, Crystallography, and Enzyme Kinetics to Reveal Plausible Steps of Isocyanide Hydratase Catalysis.Journal of chemical information and modeling · 2025Article
- Heavy-element damage seeding in proteins under XFEL illumination.Journal of synchrotron radiation · 2025Article
- An experimental proxy of water displaceability for ligand discovery.Nature methods · 2025Article
- Advances in microfluidic mixers for time-resolved structural biology with X-rays.Biophysical reviews · 2025Review
- Macromolecular crystallography and biology at the Linac Coherent Light Source.Journal of synchrotron radiation · 2025Article
- Article
- Determination of Thiol Protonation States by Sulfur X-ray Spectroscopy in Biological Systems.The journal of physical chemistry letters · 2025Article
- SFCalculator: connecting deep generative models and crystallography.bioRxiv : the preprint server for biology · 2025Article
- Exploiting fourth-generation synchrotron radiation for enzyme and photoreceptor characterization.IUCrJ · 2025Article
- Scaling and merging time-resolved pink-beam diffraction with variational inference.Structural dynamics (Melville, N.Y.) · 2024Article
- Comprehensive characterization of gas dynamic virtual nozzles for x-ray free-electron laser experiments.Structural dynamics (Melville, N.Y.) · 2024Article
- Article
- Innovative Strategies in X-ray Crystallography for Exploring Structural Dynamics and Reaction Mechanisms in Metabolic Disorders.Journal of personalized medicine · 2024Review
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Authors and funding
25 authors at 3 institutions in 2 countries.
Funding
Abstract
How changes in enzyme structure and dynamics facilitate passage along the reaction coordinate is a fundamental unanswered question. Here, we use time-resolved mix-and-inject serial crystallography (MISC) at an X-ray free electron laser (XFEL), ambient-temperature X-ray crystallography, computer simulations, and enzyme kinetics to characterize how covalent catalysis modulates isocyanide hydratase (ICH) conformational dynamics throughout its catalytic cycle. We visualize this previously hypothetical reaction mechanism, directly observing formation of a thioimidate covalent intermediate in ICH microcrystals during catalysis. ICH exhibits a concerted helical displacement upon active-site cysteine modification that is gated by changes in hydrogen bond strength between the cysteine thiolate and the backbone amide of the highly strained Ile152 residue. These catalysis-activated motions permit water entry into the ICH active site for intermediate hydrolysis. Mutations at a Gly residue (Gly150) that modulate helical mobility reduce ICH catalytic turnover and alter its pre-steady-state kinetic behavior, establishing that helical mobility is important for ICH catalytic efficiency. These results demonstrate that MISC can capture otherwise elusive aspects of enzyme mechanism and dynamics in microcrystalline samples, resolving long-standing questions about the connection between nonequilibrium protein motions and enzyme catalysis.
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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.