ArticleProceedings of the National Academy of Sciences of the United States of America2011
Large shifts in pKa values of lysine residues buried inside a protein.
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 206 papers.
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Who cites it
206 citing papers in PubMed.
- Randomized phase I trial outcomes show safe and sustainable inhibition of classical and lectin complement pathways by empasiprubart.Nature communications · 2025Trial
- Characterization of the pH-Dependent Stabilizing Forces of Insulin's Native and Fibril States.ACS physical chemistry Au · 2026Article
- Precision Chemistry for Protein Lysine Modification.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- Amino acid mediated oxidative activation of multi-walled carbon nanotubes to introduce reversible proton-coupled electron transfer species.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Article
- Molecular Origins of pH Gradients in Charge-Regulated Biomolecular Condensates.bioRxiv : the preprint server for biology · 2026Article
- Biomolecular Condensates Act as Distinct Solvation Environments That Reshape Amino Acid pJournal of the American Chemical Society · 2026Article
- Article
- Proximity-Induced Transfer of a Mass Tag Enables Direct Profiling of Active Matrix Metalloproteases.Angewandte Chemie (International ed. in English) · 2026Article
- Genetic Incorporation of Diverse Noncanonical Amino Acids for Histidine Substitution.Journal of the American Chemical Society · 2026Article
- Attempts to Achieve Targeted Covalent Inhibition of Hsp90β.Chemical biology & drug design · 2026Article
- Protein Electrostatic Properties are Finetuned Through Evolution.bioRxiv : the preprint server for biology · 2026Article
- Lysine Targeting Group-Transfer Chimeras for Proximity Induction.Angewandte Chemie (International ed. in English) · 2026Article
- Environmental Contributions to Proton Sharing in Protein Low-Barrier Hydrogen Bonds.Biochemistry · 2026Article
- Biomolecular condensates sustain pH gradients at equilibrium through charge neutralization.Nature chemistry · 2026Article
- Emergent properties of supramolecular peptide assemblies.Chemical communications (Cambridge, England) · 2026Review
- Biomolecular Condensates Act as Distinct Solvation Environments that Reshape Amino Acid pKₐ Values.bioRxiv : the preprint server for biology · 2026Article
- Co-Assemblies Regulate the Catalytic Activity of Peptide Fibrils.Angewandte Chemie (International ed. in English) · 2026Article
- Functional and Structural Characterization of Pathogenicity of Human Arginine-Histidine Variants.Journal of computational biophysics and chemistry · 2025Article
- Targeting virulence to disarm the pathogen: Enzyme-activated-substrate inhibition of Anthrax edema factor.Bioorganic & medicinal chemistry letters · 2025Article
- Molecular mechanisms and hotspots of pH sensing in ASIC1a revealed by computational and functional analysis.Communications biology · 2025Article
146 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Internal ionizable groups in proteins are relatively rare but they are essential for catalysis and energy transduction. To examine molecular determinants of their unusual and functionally important properties, we engineered 25 variants of staphylococcal nuclease with lysine residues at internal positions. Nineteen of the Lys residues have depressed pK(a) values, some as low as 5.3, and 20 titrate without triggering any detectable conformational reorganization. Apparently, simply by being buried in the protein interior, these Lys residues acquired pK(a) values comparable to those of naturally occurring internal ionizable groups involved in catalysis and biological H(+) transport. The pK(a) values of some of the internal Lys residues were affected by interactions with surface carboxylic groups. The apparent polarizability reported by the pK(a) values varied significantly from location to location inside the protein. These data will enable an unprecedented examination of the positional dependence of the dielectric response of a protein. This study also shows that the ability of proteins to withstand the presence of charges in their hydrophobic interior is a fundamental property inherent to all stable proteins, not a specialized adaptation unique to proteins that evolved to depend on internal charges for function.
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