ReviewBiophysical journal2016
What Mutagenesis Can and Cannot Reveal About Allostery.
Review in Biophysical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 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
16 citing papers in PubMed.
- Protein Surface Site Determines the Evolutionary Accessibility of Allosteric Regulation.bioRxiv : the preprint server for biology · 2026Article
- PYK-SubstitutionOME: an integrated database containing allosteric coupling, ligand affinity and mutational, structural, pathological, bioinformatic and computational information about pyruvate kinase isozymes.Database : the journal of biological databases and curation · 2023Article
- Evolution of tunnels in α/β-hydrolase fold proteins-What can we learn from studying epoxide hydrolases?PLoS computational biology · 2022Article
- Article
- The phosphate moiety of phosphoenolpyruvate does NOT contribute to allosteric regulation of liver pyruvate kinase by fructose-1,6-bisphosphateArchives of biochemistry and biophysics · 2020Article
- H/D Exchange Characterization of Silent Coupling: Entropy-Enthalpy Compensation in Allostery.Biophysical journal · 2020Article
- Functional tunability from a distance: Rheostat positions influence allosteric coupling between two distant binding sites.Scientific reports · 2019Article
- Article
- Changes in the allosteric site of human liver pyruvate kinase upon activator binding include the breakage of an intersubunit cation-π bond.Acta crystallographica. Section F, Structural biology communications · 2019Article
- Chokepoints in Mechanical Coupling Associated with Allosteric Proteins: The Pyruvate Kinase Example.Biophysical journal · 2019Article
- Modulation of allosteric coupling by mutations: from protein dynamics and packing to altered native ensembles and function.Current opinion in structural biology · 2019Review
- Glutamine Hydrolysis by Imidazole Glycerol Phosphate Synthase Displays Temperature Dependent Allosteric Activation.Frontiers in molecular biosciences · 2018Article
- An engineered photoswitchable mammalian pyruvate kinase.The FEBS journal · 2017Article
- Benchmarking predictions of allostery in liver pyruvate kinase in CAGI4.Human mutation · 2017Article
- Exploring the limits of the usefulness of mutagenesis in studies of allosteric mechanisms.Human mutation · 2017Article
- Whole-protein alanine-scanning mutagenesis of allostery: A large percentage of a protein can contribute to mechanism.Human mutation · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
2 authors.
Funding
Abstract
Allosteric regulation of protein function is recognized to be widespread throughout biology; however, knowledge of allosteric mechanisms, the molecular changes within a protein that couple one binding site to another, is limited. Although mutagenesis is often used to probe allosteric mechanisms, we consider herein what the outcome of a mutagenesis study truly reveals about an allosteric mechanism. Arguably, the best way to evaluate the effects of a mutation on allostery is to monitor the allosteric coupling constant (Qax), a ratio of the substrate binding constants in the absence versus presence of an allosteric effector. A range of substitutions at a given residue position in a protein can reveal when a particular substitution causes gain-of-function, which addresses a key challenge in interpreting mutation-dependent changes in the magnitude of Qax. Thus, whole-protein mutagenesis studies offer an acceptable means of identifying residues that contribute to an allosteric mechanism. With this focus on monitoring Qax, and keeping in mind the equilibrium nature of allostery, we consider alternative possibilities for what an allosteric mechanism might be. We conclude that different possible mechanisms (rotation-of-solid-domains, movement of secondary structure, side-chain repacking, changes in dynamics, etc.) will result in different findings in whole-protein mutagenesis studies.
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.