ArticleProteins2011
Functionally important positions can comprise the majority of a protein's architecture.
Article in Proteins, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
26 citing papers in PubMed, 35 citations in OpenAlex.
- Expanding the toolkit of LacI/GalR chimeras.PloS one · 2026Article
- Intramolecular epistasis correlates with divergence of specificity in promiscuous and bifunctional NSAR/OSBS enzymes.Protein science : a publication of the Protein Society · 2025Article
- 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
- 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
- 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
- Article
- 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
- Article
- Homolog comparisons further reconcile in vitro and in vivo correlations of protein activities by revealing over-looked physiological factors.Protein science : a publication of the Protein Society · 2019Article
- RheoScale: A tool to aggregate and quantify experimentally determined substitution outcomes for multiple variants at individual protein positions.Human mutation · 2018Article
- Lactose repressor hinge domain independently binds DNA.Protein science : a publication of the Protein Society · 2018Article
- Computational predictors fail to identify amino acid substitution effects at rheostat positions.Scientific reports · 2017Article
- Data on publications, structural analyses, and queries used to build and utilize the AlloRep database.Data in brief · 2016Article
- Using Evolution to Guide Protein Engineering: The Devil IS in the Details.Biophysical journal · 2016Review
- AlloRep: A Repository of Sequence, Structural and Mutagenesis Data for the LacI/GalR Transcription Regulators.Journal of molecular biology · 2016Article
- Article
- Flexibility and Disorder in Gene Regulation: LacI/GalR and Hox Proteins.The Journal of biological chemistry · 2015Review
- Comparative genomics and evolution of regulons of the LacI-family transcription factors.Frontiers in microbiology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Concomitant with the genomic era, many bioinformatics programs have been developed to identify functionally important positions from sequence alignments of protein families. To evaluate these analyses, many have used the LacI/GalR family and determined whether positions predicted to be "important" are validated by published experiments. However, we previously noted that predictions do not identify all of the experimentally important positions present in the linker regions of these homologs. In an attempt to reconcile these differences, we corrected and expanded the LacI/GalR sequence set commonly used in sequence/function analyses. Next, a variety of analyses were carried out (1) for the entire LacI/GalR sequence set and (2) for a subset of homologs with functionally-important "YxPxxxAxxL" motifs in their linkers. This strategy was devised to determine whether predictions could be improved by knowledge-based sequence sorting and-for some analyses-did increase the number of linker positions identified. However, two functionally important linker positions were not reliably identified by any analysis. Finally, we compared the new predictions to all known experimental data for E. coli LacI and three homologous linkers. From these, we estimate that >50% of positions are important to the functions of the LacI/GalR homologs. In corollary, neutral positions might occur less frequently and might be easier to detect in sequence analyses. Although analyses have successfully guided mutations that partially exchange protein functions, a better experimental understanding of the sequence/function relationships in protein families would be helpful for uncovering the remaining rules used by nature to evolve new protein functions.
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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.