ArticleThe Journal of biological chemistry2012
Conservation of flexible residue clusters among structural and functional enzyme homologues.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 34 citations in OpenAlex.
- Dynamics-aware evolutionary profiling uncouples structural rigidity from functional motion to enable enhanced variant interpretation.Functional & integrative genomics · 2026Article
- Conformational exchange divergence along the evolutionary pathway of eosinophil-associated ribonucleases.Structure (London, England : 1993) · 2023Article
- What the protein data bank tells us about the evolutionary conservation of protein conformational diversity.Protein science : a publication of the Protein Society · 2022Article
- Exploring the RNase A scaffold to combine catalytic and antimicrobial activities. Structural characterization of RNase 3/1 chimeras.Frontiers in molecular biosciences · 2022Article
- Thiazole-amino acids: influence of thiazole ring on conformational properties of amino acid residues.Amino acids · 2021Article
- Insights into Structural and Dynamical Changes Experienced by Human RNase 6 upon Ligand Binding.Biochemistry · 2020Article
- The Structural Dynamics of Engineered β-Lactamases Vary Broadly on Three Timescales yet Sustain Native Function.Scientific reports · 2019Article
- A Biophysical Perspective on Enzyme Catalysis.Biochemistry · 2019Article
- Evolutionary Trends in RNA Base Selectivity Within the RNase A Superfamily.Frontiers in pharmacology · 2019Article
- Conservation of Dynamics Associated with Biological Function in an Enzyme Superfamily.Structure (London, England : 1993) · 2018Article
- Why the Energy Landscape of Barnase Is Hierarchical.Frontiers in molecular biosciences · 2018Article
- Ligand-Induced Variations in Structural and Dynamical Properties Within an Enzyme Superfamily.Frontiers in molecular biosciences · 2018Article
- Sequence-specific backbone resonance assignments and microsecond timescale molecular dynamics simulation of human eosinophil-derived neurotoxin.Biomolecular NMR assignments · 2017Article
- Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily.Scientific reports · 2017Article
- Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell.Chemical reviews · 2016Review
- Role of Conformational Motions in Enzyme Function: Selected Methodologies and Case Studies.Catalysts (Basel, Switzerland) · 2016Article
- Early Folding Events, Local Interactions, and Conservation of Protein Backbone Rigidity.Biophysical journal · 2016Article
- Perturbation of the Conformational Dynamics of an Active-Site Loop Alters Enzyme Activity.Structure (London, England : 1993) · 2015Article
- Carboxylated acyclonucleosides: synthesis and RNase A inhibition.Molecules (Basel, Switzerland) · 2015Article
- Network of long-range concerted chemical shift displacements upon ligand binding to human angiogenin.Protein science : a publication of the Protein Society · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Conformational flexibility between structural ensembles is an essential component of enzyme function. Although the broad dynamical landscape of proteins is known to promote a number of functional events on multiple time scales, it is yet unknown whether structural and functional enzyme homologues rely on the same concerted residue motions to perform their catalytic function. It is hypothesized that networks of contiguous and flexible residue motions occurring on the biologically relevant millisecond time scale evolved to promote and/or preserve optimal enzyme catalysis. In this study, we use a combination of NMR relaxation dispersion, model-free analysis, and ligand titration experiments to successfully capture and compare the role of conformational flexibility between two structural homologues of the pancreatic ribonuclease family: RNase A and eosinophil cationic protein (or RNase 3). In addition to conserving the same catalytic residues and structural fold, both homologues show similar yet functionally distinct clusters of millisecond dynamics, suggesting that conformational flexibility can be conserved among analogous protein folds displaying low sequence identity. Our work shows that the reduced conformational flexibility of eosinophil cationic protein can be dynamically and functionally reproduced in the RNase A scaffold upon creation of a chimeric hybrid between the two proteins. These results support the hypothesis that conformational flexibility is partly required for catalytic function in homologous enzyme folds, further highlighting the importance of dynamic residue sectors in the structural organization of proteins.
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.