ArticleStructure (London, England : 1993)2014
Crystal cryocooling distorts conformational heterogeneity in a model Michaelis complex of DHFR.
Article in Structure (London, England : 1993), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
104 citing papers in PubMed.
- Structural insights into urocanate reductase using room-temperature X-ray crystallography.Acta crystallographica. Section D, Structural biology · 2026Article
- Structural insights into RNase H catalytic mechanism from room-temperature X-ray and neutron crystallography of apo- and RNA/DNA hybrid-bound enzyme.Current research in structural biology · 2026Article
- Unfreezing structural biology for drug discovery.Nature chemical biology · 2026Review
- Advances in Crystallography and Cryo-Electron Microscopy for the Study of Membrane Proteins.Advances in experimental medicine and biology · 2026Review
- Binding mode of Isoxazolyl Penicillins to a Class-A β-lactamase at ambient conditions.Communications chemistry · 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
- Article
- 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
- An experimental proxy of water displaceability for ligand discovery.Nature methods · 2025Article
- Status and perspective of protein crystallography at the first multi-bend achromat based synchrotron MAX IV.Journal of synchrotron radiation · 2025Article
- Revealing Functional Hotspots: Temperature-Dependent Crystallography of K-RAS Highlights Allosteric and Druggable Sites.bioRxiv : the preprint server for biology · 2025Article
- Differential Responses in the Core, Active Site and Peripheral Regions of Cytochrome c Peroxidase to Extreme Pressure and Temperature.Journal of molecular biology · 2024Article
- Exploring the dynamics of allostery through multi-dimensional crystallography.Biophysical reviews · 2024Review
- An expanded trove of fragment-bound structures for the allosteric enzyme PTP1B from computational reanalysis of large-scale crystallographic data.Structure (London, England : 1993) · 2024Article
- Changes in an enzyme ensemble during catalysis observed by high-resolution XFEL crystallography.Science advances · 2024Article
- Predicted and Experimental NMR Chemical Shifts at Variable Temperatures: The Effect of Protein Conformational Dynamics.The journal of physical chemistry letters · 2024Review
- Perturbative diffraction methods resolve a conformational switch that facilitates a two-step enzymatic mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Contribution of protein conformational heterogeneity to NMR lineshapes at cryogenic temperatures.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Most macromolecular X-ray structures are determined from cryocooled crystals, but it is unclear whether cryocooling distorts functionally relevant flexibility. Here we compare independently acquired pairs of high-resolution data sets of a model Michaelis complex of dihydrofolate reductase (DHFR), collected by separate groups at both room and cryogenic temperatures. These data sets allow us to isolate the differences between experimental procedures and between temperatures. Our analyses of multiconformer models and time-averaged ensembles suggest that cryocooling suppresses and otherwise modifies side-chain and main-chain conformational heterogeneity, quenching dynamic contact networks. Despite some idiosyncratic differences, most changes from room temperature to cryogenic temperature are conserved and likely reflect temperature-dependent solvent remodeling. Both cryogenic data sets point to additional conformations not evident in the corresponding room temperature data sets, suggesting that cryocooling does not merely trap preexisting conformational heterogeneity. Our results demonstrate that crystal cryocooling consistently distorts the energy landscape of DHFR, a paragon for understanding functional protein dynamics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.