ArticleProteins2020
Identification of biochemically neutral positions in liver pyruvate kinase.
Article in Proteins, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Amino acid substitutions at rheostat positions in the NaProtein science : a publication of the Protein Society · 2025Article
- Dissecting the effects of single amino acid substitutions in SARS-CoV-2 Mpro.Protein science : a publication of the Protein Society · 2025Article
- Identification of positions in human aldolase a that are neutral for apparent KArchives of biochemistry and biophysics · 2024Article
- Dynamics-based protein network features accurately discriminate neutral and rheostat positions.Biophysical journal · 2024Article
- Rheostatic contributions to protein stability can obscure a position's functional role.Protein science : a publication of the Protein Society · 2024Article
- Rheostats, toggles, and neutrals, Oh my! A new framework for understanding how amino acid changes modulate protein function.The Journal of biological chemistry · 2024Review
- The intrinsically disordered transcriptional activation domain of CIITA is functionally tuneable by single substitutions: An exception or a new paradigm?Protein science : a publication of the Protein Society · 2024Article
- The 2.4 Å structure of Zymomonas mobilis pyruvate kinase: Implications for stability and regulation.Archives of biochemistry and biophysics · 2023Article
- 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
- VariBench, new variation benchmark categories and data sets.Frontiers in bioinformatics · 2023Article
- Odd one out? Functional tuning of Zymomonas mobilis pyruvate kinase is narrower than its allosteric, human counterpart.Protein science : a publication of the Protein Society · 2022Article
- Structural Plasticity Is a Feature of Rheostat Positions in the Human NaInternational journal of molecular sciences · 2022Article
- Substitutions at a rheostat position in human aldolase A cause a shift in the conformational population.Protein science : a publication of the Protein Society · 2022Article
- Rheostat functional outcomes occur when substitutions are introduced at nonconserved positions that diverge with speciation.Protein science : a publication of the Protein Society · 2021Article
- Substitutions at Nonconserved Rheostat Positions Modulate Function by Rewiring Long-Range, Dynamic Interactions.Molecular biology and evolution · 2021Article
- Rheostat positions: A new classification of protein positions relevant to pharmacogenomics.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2020Article
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 at 1 institution in 1 country.
Funding
Abstract
Understanding how each residue position contributes to protein function has been a long-standing goal in protein science. Substitution studies have historically focused on conserved protein positions. However, substitutions of nonconserved positions can also modify function. Indeed, we recently identified nonconserved positions that have large substitution effects in human liver pyruvate kinase (hLPYK), including altered allosteric coupling. To facilitate a comparison of which characteristics determine when a nonconserved position does vs does not contribute to function, the goal of the current work was to identify neutral positions in hLPYK. However, existing hLPYK data showed that three features commonly associated with neutral positions-high sequence entropy, high surface exposure, and alanine scanning-lacked the sensitivity needed to guide experimental studies. We used multiple evolutionary patterns identified in a sequence alignment of the PYK family to identify which positions were least patterned, reasoning that these were most likely to be neutral. Nine positions were tested with a total of 117 amino acid substitutions. Although exploring all potential functions is not feasible for any protein, five parameters associated with substrate/effector affinities and allosteric coupling were measured for hLPYK variants. For each position, the aggregate functional outcomes of all variants were used to quantify a "neutrality" score. Three positions showed perfect neutral scores for all five parameters. Furthermore, the nine positions showed larger neutral scores than 17 positions located near allosteric binding sites. Thus, our strategy successfully enriched the dataset for positions with neutral and modest substitutions.
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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.