ArticleeLife2015
Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed.
- Separating the effects of temperature and absorbed X-ray dose on unit-cell volume.Acta crystallographica. Section D, Structural biology · 2026Article
- Putrescine-bound structure and multi-temperature crystallography provide new insights into ligand binding and conformational heterogeneity in spermidine synthase.Structural dynamics (Melville, N.Y.) · 2026Article
- Activation parameters, enthalpy-entropy compensation and the temperature-dependent activity of enzymes.Protein science : a publication of the Protein Society · 2026Article
- An integrated experimental and computational pipeline for crystallographic fragment screening of membrane protein in the lipid cubic phase.Communications chemistry · 2026Article
- Statistical crystallography reveals an allosteric network in SARS-CoV-2 MCommunications biology · 2026Article
- Thiol post-translational modifications modulate allosteric regulation of the OpcA-G6PDH complex through conformational gate control.Protein science : a publication of the Protein Society · 2026Article
- Loop dynamics, allostery, and function in protein tyrosine phosphatases: insights from molecular simulations.Biochemical Society transactions · 2026Review
- Hydrogen-deuterium exchange reveals catalytically linked protein flexibility in myoglobin-mediated intramolecular C(spProtein science : a publication of the Protein Society · 2026Article
- Towards patient-relevant structures: reviewing body-temperature biological macromolecules and their ligands for pharmaceutical applications.Acta crystallographica. Section D, Structural biology · 2026Review
- Sensitive detection of structural dynamics using a statistical framework for comparative crystallography.Science advances · 2025Article
- Article
- Denoising and iterative phase recovery reveal low-occupancy populations in protein crystals.Communications biology · 2025Article
- Activation parameters, enthalpy-entropy compensation and the temperature-dependent activity of enzymes.bioRxiv : the preprint server for biology · 2025Article
- Bayesian multi-state multi-condition modeling of a protein structure based on X-ray crystallography data.bioRxiv : the preprint server for biology · 2025Article
- Multi-Temperature Crystallography of S-Adenosylmethionine Decarboxylase Observes Dynamic Loop Motions.Biomolecules · 2025Article
- Probing the modulation of enzyme kinetics by multi-temperature, time-resolved serial crystallography.Nature communications · 2025Article
- Structure-Based Experimental Datasets for Benchmarking Protein Simulation Force Fields [Article v1.0].Living journal of computational molecular science · 2025Article
- Protein Catalysis Through Structural Dynamics: A Comprehensive Analysis of Energy Conversion in Enzymatic Systems and Its Computational Limitations.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A Foundational Shift in Models for Enzyme Function.Journal of the American Chemical Society · 2025Review
- Review
59 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors.
Funding
Abstract
Determining the interconverting conformations of dynamic proteins in atomic detail is a major challenge for structural biology. Conformational heterogeneity in the active site of the dynamic enzyme cyclophilin A (CypA) has been previously linked to its catalytic function, but the extent to which the different conformations of these residues are correlated is unclear. Here we compare the conformational ensembles of CypA by multitemperature synchrotron crystallography and fixed-target X-ray free-electron laser (XFEL) crystallography. The diffraction-before-destruction nature of XFEL experiments provides a radiation-damage-free view of the functionally important alternative conformations of CypA, confirming earlier synchrotron-based results. We monitored the temperature dependences of these alternative conformations with eight synchrotron datasets spanning 100-310 K. Multiconformer models show that many alternative conformations in CypA are populated only at 240 K and above, yet others remain populated or become populated at 180 K and below. These results point to a complex evolution of conformational heterogeneity between 180--240 K that involves both thermal deactivation and solvent-driven arrest of protein motions in the crystal. The lack of a single shared conformational response to temperature within the dynamic active-site network provides evidence for a conformation shuffling model, in which exchange between rotamer states of a large aromatic ring in the middle of the network shifts the conformational ensemble for the other residues in the network. Together, our multitemperature analyses and XFEL data motivate a new generation of temperature- and time-resolved experiments to structurally characterize the dynamic underpinnings of protein function.
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