ArticleJournal of molecular biology2009
The pK(a) values of acidic and basic residues buried at the same internal location in a protein are governed by different factors.
Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 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
69 citing papers in PubMed, 153 citations in OpenAlex.
- Modulating Radical Propagation in Proteins by Proton-Coupled Electron Transfer and Hydrogen Bonding.Biochemistry · 2026Article
- Site-specific phosphorylation of Ser352 drives aggregation of Tau R4 under acidosis conditions.Chemical science · 2026Article
- Electrostatics and disease: Large-scale assessment of human missense variants causing protein charge alterations and their implications for disease.Biophysical journal · 2026Article
- Characterization of blood-brain barrier L-arginine uptake using in situ brain perfusions in a female mouse model.Fluids and barriers of the CNS · 2026Article
- Computational Study of Arsenite Binding to Tetraglycine: Structural and Energetic Insights.Chemistry, an Asian journal · 2026Article
- Protonated Structure of EmrE Reveals C-terminal Tail Gating Mechanism.bioRxiv : the preprint server for biology · 2026Article
- Modulating radical propagation in proteins by proton-coupled electron transfer and hydrogen bonding.bioRxiv : the preprint server for biology · 2026Article
- PKAD-R: curated, redesigned and expanded database of experimental pKa values in proteins.Journal of computational biophysics and chemistry · 2025Article
- Survival of Thermostable Φ6 Genotypes in Acidic, Basic, and UV Environments.bioRxiv : the preprint server for biology · 2025Article
- Advancing Covalent Ligand and Drug Discovery beyond Cysteine.Chemical reviews · 2025Review
- Coacervate-Based Delivery Systems: Bridging Fundamentals and Applications.ACS applied materials & interfaces · 2025Review
- Enhancing Cold Adaptation of Bidomain Amylases by High-Throughput Computational Engineering.Angewandte Chemie (International ed. in English) · 2025Article
- Selective Inhibitor Design against Thymidylate Synthase ofACS omega · 2025Article
- Acetylation-Dependent Compaction of the Histone H4 Tail Ensemble.The journal of physical chemistry. B · 2024Article
- Advancing protein therapeutics through proximity-induced chemistry.Cell chemical biology · 2024Review
- Accurately Predicting Protein pJournal of chemical theory and computation · 2023Article
- Article
- AMOEBA Force Field Predicts Accurate Hydrogen Bond Counts of Nitriles in SNase by Revealing Water-Protein Interaction in Vibrational Absorption Frequencies.The journal of physical chemistry. B · 2023Article
- Critical Beginnings: Selective Tuning of Solubility and Structural Accuracy of Newly Synthesized Proteins by the Hsp70 Chaperone System.The journal of physical chemistry. B · 2023Article
- Electrostatic interactions mediate the nucleation and growth of a bacterial functional amyloid.Frontiers in molecular biosciences · 2023Article
9 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
7 authors at 2 institutions in 1 country.
Funding
Abstract
The pK(a) values of internal ionizable groups are usually very different from the normal pK(a) values of ionizable groups in water. To examine the molecular determinants of pK(a) values of internal groups, we compared the properties of Lys, Asp, and Glu at internal position 38 in staphylococcal nuclease. Lys38 titrates with a normal or elevated pK(a), whereas Asp38 and Glu38 titrate with elevated pK(a) values of 7.0 and 7.2, respectively. In the structure of the L38K variant, the buried amino group of the Lys38 side chain makes an ion pair with Glu122, whereas in the structure of the L38E variant, the buried carboxyl group of Glu38 interacts with two backbone amides and has several nearby carboxyl oxygen atoms. Previously, we showed that the pK(a) of Lys38 is normal owing to structural reorganization and water penetration concomitant with ionization of the Lys side chain. In contrast, the pK(a) values of Asp38 and Glu38 are perturbed significantly owing to an imbalance between favorable polar interactions and unfavorable contributions from dehydration and from Coulomb interactions with surface carboxylic groups. Their ionization is also coupled to subtle structural reorganization. These results illustrate the complex interplay between local polarity, Coulomb interactions, and structural reorganization as determinants of pK(a) values of internal groups in proteins. This study suggests that improvements to computational methods for pK(a) calculations will require explicit treatment of the conformational reorganization that can occur when internal groups ionize.
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.