ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structural and thermodynamic consequences of burial of an artificial ion pair in the hydrophobic interior of a protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
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- Cryo-EM structures of ALECT2 filaments from human renal biopsies.Nature communications · 2026Article
- Dissected antiporter modules establish minimal proton-conduction elements of the respiratory complex I.Nature communications · 2024Article
- Telodendrimer functionalized hydrogel platform for sustained antibiotics release in infection control.Acta biomaterialia · 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
- Enhanced Sampling of Buried Charges in Free Energy Calculations Using Replica Exchange with Charge Tempering.Journal of chemical theory and computation · 2024Article
- Electronic Polarization Is Essential for the Stabilization and Dynamics of Buried Ion Pairs in Staphylococcal Nuclease Mutants.Journal of the American Chemical Society · 2022Article
- De Novo Design of a Highly Stable Ovoid TIM Barrel: Unlocking Pocket Shape towards Functional Design.Biodesign research · 2022Article
- Structural basis of the protochromic green/red photocycle of the chromatic acclimation sensor RcaE.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Design of buried charged networks in artificial proteins.Nature communications · 2021Article
- Immobilized Crosslinked Pectinase Preparation on Porous ZSM-5 Zeolites as Reusable Biocatalysts for Ultra-Efficient Hydrolysis of β-Glycosidic Bonds.Frontiers in chemistry · 2021Article
- The relative stability of trpzip1 and its mutants determined by computation and experiment.RSC advances · 2020Article
- Article
- Sequencing and Structural Analysis of the Complete Chloroplast Genome of the Medicinal PlantPlants (Basel, Switzerland) · 2019Article
- Hydronium Ions Accompanying Buried Acidic Residues Lead to High Apparent Dielectric Constants in the Interior of Proteins.The journal of physical chemistry. B · 2018Article
- Driving Forces of Translocation Through Bacterial Translocon SecYEG.The Journal of membrane biology · 2018Article
- Combinatorial approaches in post-polymerization modification for rational development of therapeutic delivery systems.Acta biomaterialia · 2018Review
- Polycation-telodendrimer nanocomplexes for intracellular protein delivery.Colloids and surfaces. B, Biointerfaces · 2018Article
- An Internal Disulfide Locks a Misfolded Aggregation-prone Intermediate in Cataract-linked Mutants of Human γD-Crystallin.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
An artificial charge pair buried in the hydrophobic core of staphylococcal nuclease was engineered by making the V23E and L36K substitutions. Buried individually, Glu-23 and Lys-36 both titrate with pKa values near 7. When buried together their pKa values appear to be normal. The ionizable moieties of the buried Glu-Lys pair are 2.6 Å apart. The interaction between them at pH 7 is worth 5 kcal/mol. Despite this strong interaction, the buried Glu-Lys pair destabilizes the protein significantly because the apparent Coulomb interaction is sufficient to offset the dehydration of only one of the two buried charges. Save for minor reorganization of dipoles and water penetration consistent with the relatively high dielectric constant reported by the buried ion pair, there is no evidence that the presence of two charges in the hydrophobic interior of the protein induces any significant structural reorganization. The successful engineering of an artificial ion pair in a highly hydrophobic environment suggests that buried Glu-Lys pairs in dehydrated environments can be charged and that it is possible to engineer charge clusters that loosely resemble catalytic sites in a scaffold protein with high thermodynamic stability, without the need for specialized structural adaptations.
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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.