ArticleProceedings of the National Academy of Sciences of the United States of America2010
Charges in the hydrophobic interior of proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 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
102 citing papers in PubMed.
- Disease-Associated Mutations Impact DNA Methyltransferase 1 Function through Dynamic Allosteric Effects and Solvent Exposure.Journal of chemical theory and computation · 2026Article
- Moderate moisture evaporation strengthens the network structure and practical features of konjac glucomannan/soy protein isolate system during drying process.Food chemistry: X · 2026Article
- Protein Electrostatic Properties are Finetuned Through Evolution.bioRxiv : the preprint server for biology · 2026Article
- Emergent properties of supramolecular peptide assemblies.Chemical communications (Cambridge, England) · 2026Review
- HDX-MS reveals pH and temperature-responsive regions on AAV capsids and the structural basis for DNA release.Gene therapy · 2025Article
- Conduction pathway for potassium through theeLife · 2025Article
- PKAD-R: curated, redesigned and expanded database of experimental pKa values in proteins.Journal of computational biophysics and chemistry · 2025Article
- Conduction pathway for potassium through the E. coli pump KdpFABC.bioRxiv : the preprint server for biology · 2025Article
- KaMLs for Predicting Protein pJournal of chemical theory and computation · 2025Article
- Hexokinase-I directly binds to a charged membrane-buried glutamate of mitochondrial VDAC1 and VDAC2.Communications biology · 2025Article
- Improved Structure-Based Histidine pJournal of chemical information and modeling · 2025Article
- KaMLs for Predicting Protein pbioRxiv : the preprint server for biology · 2025Article
- Development of artificial photosystems based on designed proteins for mechanistic insights into photosynthesis.Protein science : a publication of the Protein Society · 2024Review
- Protecting Proteins from Desiccation Stress Using Molecular Glasses and Gels.Chemical reviews · 2024Review
- Accurately Predicting Protein pJournal of chemical theory and computation · 2023Article
- Energy coupling and stoichiometry of ZneLife · 2023Article
- Not Always Sticky: Specificity of Protein Stabilization by Sugars Is Conferred by Protein-Water Hydrogen Bonds.Journal of the American Chemical Society · 2023Article
- SARS-CoV-2 fusion peptide sculpting of a membrane with insertion of charged and polar groups.Structure (London, England : 1993) · 2023Article
- The cofactor-dependent folding mechanism of Drosophila cryptochrome revealed by single-molecule pulling experiments.Nature communications · 2023Article
- Far-Field Electrostatic Signatures of Macromolecular 3D Conformation.Nano letters · 2022Article
42 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
5 authors.
Funding
Abstract
Charges are inherently incompatible with hydrophobic environments. Presumably for this reason, ionizable residues are usually excluded from the hydrophobic interior of proteins and are found instead at the surface, where they can interact with bulk water. Paradoxically, ionizable groups buried in the hydrophobic interior of proteins play essential roles, especially in biological energy transduction. To examine the unusual properties of internal ionizable groups we measured the pK(a) of glutamic acid residues at 25 internal positions in a stable form of staphylococcal nuclease. Two of 25 Glu residues titrated with normal pK(a) near 4.5; the other 23 titrated with elevated pK(a) values ranging from 5.2-9.4, with an average value of 7.7. Trp fluorescence and far-UV circular dichroism were used to monitor the effects of internal charges on conformation. These data demonstrate that although charges buried in proteins are indeed destabilizing, charged side chains can be buried readily in the hydrophobic core of stable proteins without the need for specialized structural adaptations to stabilize them, and without inducing any major conformational reorganization. The apparent dielectric effect experienced by the internal charges is considerably higher than the low dielectric constants of hydrophobic matter used to represent the protein interior in electrostatic continuum models of proteins. The high thermodynamic stability required for proteins to withstand the presence of buried charges suggests a pathway for the evolution of enzymes, and it underscores the need to mind thermodynamic stability in any strategy for engineering novel or altered enzymatic active sites in 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.