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Structural and thermodynamic consequences of burial of an artificial ion pair in the hydrophobic interior of a protein.

Robinson AC, Castañeda CA, Schlessman JL, García-Moreno EB
Proc Natl Acad Sci U S A 111 11685-90 (2014)
Cited: 20 times
EuropePMC logo PMID: 25074910

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.

Articles - 3qol mentioned but not cited (1)

  1. Structural and thermodynamic consequences of burial of an artificial ion pair in the hydrophobic interior of a protein. Robinson AC, Castañeda CA, Schlessman JL, García-Moreno EB. Proc Natl Acad Sci U S A 111 11685-11690 (2014)


Reviews citing this publication (1)

  1. Combinatorial approaches in post-polymerization modification for rational development of therapeutic delivery systems. Zhong Y, Zeberl BJ, Wang X, Luo J. Acta Biomater 73 21-37 (2018)

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  2. Affinity-controlled protein encapsulation into sub-30 nm telodendrimer nanocarriers by multivalent and synergistic interactions. Wang X, Shi C, Zhang L, Bodman A, Guo D, Wang L, Hall WA, Wilkens S, Luo J. Biomaterials 101 258-271 (2016)
  3. q-Canonical Monte Carlo Sampling for Modeling the Linkage between Charge Regulation and Conformational Equilibria of Peptides. Fossat MJ, Pappu RV. J Phys Chem B 123 6952-6967 (2019)
  4. Sequencing and Structural Analysis of the Complete Chloroplast Genome of the Medicinal Plant Lyciumchinense Mill. Yang Z, Huang Y, An W, Zheng X, Huang S, Liang L. Plants (Basel) 8 E87 (2019)
  5. A Detailed Analysis of the Morphology of Fibrils of Selectively Mutated Amyloid β (1-40). Adler J, Baumann M, Voigt B, Scheidt HA, Bhowmik D, Häupl T, Abel B, Madhu PK, Balbach J, Maiti S, Huster D. Chemphyschem 17 2744-2753 (2016)
  6. Effect of a buried ion pair in the hydrophobic core of a protein: An insight from constant pH molecular dynamics study. Pathak AK. Biopolymers 103 148-157 (2015)
  7. Structural basis of the protochromic green/red photocycle of the chromatic acclimation sensor RcaE. Nagae T, Unno M, Koizumi T, Miyanoiri Y, Fujisawa T, Masui K, Kamo T, Wada K, Eki T, Ito Y, Hirose Y, Mishima M. Proc Natl Acad Sci U S A 118 e2024583118 (2021)
  8. Polycation-telodendrimer nanocomplexes for intracellular protein delivery. Wang X, Shi C, Wang L, Luo J. Colloids Surf B Biointerfaces 162 405-414 (2018)
  9. Design of buried charged networks in artificial proteins. Baumgart M, Röpke M, Mühlbauer ME, Asami S, Mader SL, Fredriksson K, Groll M, Gamiz-Hernandez AP, Kaila VRI. Nat Commun 12 1895 (2021)
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  15. De Novo Design of a Highly Stable Ovoid TIM Barrel: Unlocking Pocket Shape towards Functional Design. Chu AE, Fernandez D, Liu J, Eguchi RR, Huang PS. Biodes Res 2022 9842315 (2022)
  16. Electronic Polarization Is Essential for the Stabilization and Dynamics of Buried Ion Pairs in Staphylococcal Nuclease Mutants. Deng J, Cui Q. J Am Chem Soc 144 4594-4610 (2022)
  17. Immobilized Crosslinked Pectinase Preparation on Porous ZSM-5 Zeolites as Reusable Biocatalysts for Ultra-Efficient Hydrolysis of β-Glycosidic Bonds. Liu C, Zhang L, Tan L, Liu Y, Tian W, Ma L. Front Chem 9 677868 (2021)
  18. Salt bridge as a gatekeeper against partial unfolding. Hinzman MW, Essex ME, Park C. Protein Sci 25 999-1009 (2016)


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