ArticleProceedings of the National Academy of Sciences of the United States of America2011
Arginine residues at internal positions in a protein are always charged.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 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
95 citing papers in PubMed, 184 citations in OpenAlex.
- Modulating Radical Propagation in Proteins by Proton-Coupled Electron Transfer and Hydrogen Bonding.Biochemistry · 2026Article
- Propionic acidemia in Mexico: Clinical and genotypic spectrum.Molecular genetics and metabolism reports · 2026Article
- Modulating radical propagation in proteins by proton-coupled electron transfer and hydrogen bonding.bioRxiv : the preprint server for biology · 2026Article
- Article
- Solvent Channels and Electric Fields Guide Proton Delivery to the Active Site of Heme Peroxidases.Angewandte Chemie (International ed. in English) · 2025Article
- Article
- Charge Neutralization During Peptide Transport in the Bacterial SecYEG Translocon.Biomolecules · 2025Article
- Revealing the glutamate switch: Insights into proton translocation in plant HBiophysical journal · 2025Article
- Arginine: I. Interactions of Its Guanidinium Moiety with Branched Aliphatic Side Chains.The journal of physical chemistry. B · 2025Article
- Arginine: II. Interactions of Its Salt Bridges with Branched Aliphatic Side Chains.The journal of physical chemistry. B · 2025Article
- A pH-Centric Model of Nucleolar Activity and Regulation.Journal of molecular biology · 2025Review
- Oculocutaneous albinism in a patient with anAsian biomedicine : research, reviews and news · 2025Article
- Stabilization of the catalytically active structure of a molybdenum-dependent formate dehydrogenase depends on a highly conserved lysine residue.The FEBS journal · 2025Article
- Maillard Reaction: Mechanism, Influencing Parameters, Advantages, Disadvantages, and Food Industrial Applications: A Review.Foods (Basel, Switzerland) · 2025Review
- Synthesis of SelectivelyChemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Arginine: at the crossroads of nitrogen metabolism.The EMBO journal · 2025Review
- MEDOC: A Fast, Scalable, and Mathematically Exact Algorithm for the Site-Specific Prediction of the Protonation Degree in Large Disordered Proteins.Journal of chemical information and modeling · 2025Article
- Complete defect in PA-PLAFrontiers in genetics · 2025Article
- Solvent-Dependent Chemoselectivity Switch to Arg-Lys Imidazole Cross-Links.Organic letters · 2024Article
- Aromatic Residues in Proteins: Re-Evaluating the Geometry and Energetics of π-π, Cation-π, and CH-π Interactions.The journal of physical chemistry. B · 2024Article
35 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
Many functionally essential ionizable groups are buried in the hydrophobic interior of proteins. A systematic study of Lys, Asp, and Glu residues at 25 internal positions in staphylococcal nuclease showed that their pK(a) values can be highly anomalous, some shifted by as many as 5.7 pH units relative to normal pK(a) values in water. Here we show that, in contrast, Arg residues at the same internal positions exhibit no detectable shifts in pK(a); they are all charged at pH ≤ 10. Twenty-three of these 25 variants with Arg are folded at both pH 7 and 10. The mean decrease in thermodynamic stability from substitution with Arg was 6.2 kcal/mol at this pH, comparable to that for substitution with Lys, Asp, or Glu at pH 7. The physical basis behind the remarkable ability of Arg residues to remain protonated in environments otherwise incompatible with charges is suggested by crystal structures of three variants showing how the guanidinium moiety of the Arg side chain is effectively neutralized through multiple hydrogen bonds to protein polar atoms and to site-bound water molecules. The length of the Arg side chain, and slight deformations of the protein, facilitate placement of the guanidinium moieties near polar groups or bulk water. This unique capacity of Arg side chains to retain their charge in dehydrated environments likely contributes toward the important functional roles of internal Arg residues in situations where a charge is needed in the interior of a protein, in a lipid bilayer, or in similarly hydrophobic environments.
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.