Almost all proteins contain charged amino acids. While the function in catalysis or binding of individual charges in the active site can often be identified, it is less clear how to assign function to charges beyond this region. Are they necessary for solubility? For reasons other than solubility? Can manipulating these charges change the properties of proteins? A combination of capillary electrophoresis (CE) and protein charge ladders makes it possible to study the roles of charged residues on the surface of proteins outside the active site. This method involves chemical modification of those residues to generate a large number of derivatives of the protein that differ in charge. CE separates those derivatives into groups with the same number of modified charged groups. By studying the influence of charge on the properties of proteins using charge ladders, it is possible to estimate the net charge and hydrodynamic radius and to infer the role of charged residues in ligand binding and protein folding.
Looking at proteins: representations, folding, packing, and design. Biophysical Society National Lecture, 1992
Solvent-induced conformational changes of polypeptides probed by electrospray-ionization mass spectrometry
Structural and thermodynamic consequences of burying a charged residue within the hydrophobic core of T4 lysozyme
Contributions of engineered surface salt bridges to the stability of T4 lysozyme determined by directed mutagenesis
pH-induced denaturation of proteins: a single salt bridge contributes 3-5 kcal/mol to the free energy of folding of T4 lysozyme
Inter- and intramolecular reactions of alpha-lactalbumin. VII. The hydrogen ion titration curve of alpha-lactalbumin
Analysis of the pH dependence of the neonatal Fc receptor/immunoglobulin G interaction using antibody and receptor variants
Quantitative analysis of conformational equilibrium using capillary electrophoresis: applications to protein folding
Mapping the structures of transition states and intermediates in folding: delineation of pathways at high resolution
Comparison of the conformational stability of the molten globule and native states of horse cytochrome c. Effects of acetylation, heat, urea and guanidine-hydrochloride
Contribution of long-range electrostatic interactions to the stabilization of the catalytic transition state of the serine protease subtilisin BPN'
Long-range surface charge-charge interactions in proteins. Comparison of experimental results with calculations from a theoretical method
Use of affinity capillary electrophoresis to determine kinetic and equilibrium constants for binding of arylsulfonamides to bovine carbonic anhydrase
Using capillary electrophoresis to follow the acetylation of the amino groups of insulin and to estimate their basicities
Energy considerations show that low-barrier hydrogen bonds do not offer a catalytic advantage over ordinary hydrogen bonds
Using protein charge ladders to estimate the effective charges and molecular weights of proteins in solution
Representing primary electrophoretic data in the 1/time domain: comparison to representations in the time domain
Electrostatic effects on protein partitioning in size-exclusion chromatography and membrane ultrafiltration
Affinity capillary electrophoresis: a physical-organic tool for studying interactions in biomolecular recognition
The role of charged residues mediating low affinity protein-protein recognition at the cell surface by CD2
Stable cationic capillary coating with successive multiple ionic polymer layers for capillary electrophoresis
Buried, charged, non-ion-paired aspartic acid 76 contributes favorably to the conformational stability of ribonuclease T1
Realistic modeling of the denatured states of proteins allows accurate calculations of the pH dependence of protein stability
Essential role of a single arginine of photosystem I in stabilizing the electron transfer complex with ferredoxin
Electrostatic strengths of salt bridges in thermophilic and mesophilic glutamate dehydrogenase monomers
Fluctuations between stabilizing and destabilizing electrostatic contributions of ion pairs in conformers of the c-Myc-Max leucine zipper
Determination of effective protein charge by capillary electrophoresis: effects of charge regulation in the analysis of charge ladders
Calculation of weak protein-protein interactions: the pH dependence of the second virial coefficient
Measuring the size and charge of proteins using protein charge ladders, capillary electrophoresis, and electrokinetic models of colloids
Contribution of aromatic-aromatic interactions to the anomalous pK(a) of tyrosine-9 and the C-terminal dynamics of glutathione S-transferase A1-1
The chemical modification of alpha-chymotrypsin with both hydrophobic and hydrophilic compounds stabilizes the enzyme against denaturation in water-organic media
Rationally designed mutations convert de novo amyloid-like fibrils into monomeric beta-sheet proteins
Analysis by capillary electrophoresis of the kinetics of charge ladder formation for bovine carbonic anhydrase
Rational cytokine design for increased lifetime and enhanced potency using pH-activated "histidine switching"
Studies of the aggregation of mutant proteins in vitro provide insights into the genetics of amyloid diseases
The structure of bovine lysosomal alpha-mannosidase suggests a novel mechanism for low-pH activation
Contributions of mass spectrometry in the study of nucleic acid-binding proteins and of nucleic acid-protein interactions
Comparison of calculation and experiment implicates significant electrostatic contributions to the binding stability of barnase and barstar
pH dependence and stoichiometry of binding to the Fc region of IgG by the herpes simplex virus Fc receptor gE-gI
Escherichia coli glutaminyl-tRNA synthetase is electrostatically optimized for binding of its cognate substrates
Benzoyl derivatization as a method to improve retention of hydrophilic peptides in tryptic peptide mapping
Electrostatic contributions to protein retention in ion-exchange chromatography. 1. Cytochrome C variants
Diffusivity of solutes measured in glass capillaries using Taylor's analysis of dispersion and a commercial CE instrument
Thermodynamic stability of carbonic anhydrase: measurements of binding affinity and stoichiometry using ThermoFluor
Eliminating positively charged lysine epsilon-NH3+ groups on the surface of carbonic anhydrase has no significant influence on its folding from sodium dodecyl sulfate
Electrostatic potential of aminoacyl-tRNA synthetase navigates tRNA on its pathway to the binding site
Effect of background electrolyte on the estimation of protein hydrodynamic radius and net charge through capillary zone electrophoresis
Size and charge characterization of polymeric drug delivery systems by Taylor dispersion analysis and capillary electrophoresis
Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding
Complexes of native ubiquitin and dodecyl sulfate illustrate the nature of hydrophobic and electrostatic interactions in the binding of proteins and surfactants
Neutralizing positive charges at the surface of a protein lowers its rate of amide hydrogen exchange without altering its structure or increasing its thermostability
Influence of fluorocarbon and hydrocarbon acyl groups at the surface of bovine carbonic anhydrase II on the kinetics of denaturation by sodium dodecyl sulfate
Insights into the evolution of the CSP gene family through the integration of evolutionary analysis and comparative protein modeling
Electrostatic attraction between cationic-anionic assemblies with surface compositional heterogeneities
Thermodynamics of ternary electrolytes: Enhanced adsorption of macroions as minority component to liquid interfaces
Fast, Label-Free Tracking of Single Viruses and Weakly Scattering Nanoparticles in a Nanofluidic Optical Fiber
Oligomeric state and structural stability of two hyperthermophilic β-glucosidases from Thermotoga petrophila
The effects of alternating electric fields in glioblastoma: current evidence on therapeutic mechanisms and clinical outcomes
Acetylation of Surface Lysine Groups of a Protein Alters the Organization and Composition of Its Crystal Contacts
Artificial Modification of an Enzyme for Construction of Cross-Reactive Polyion Complexes To Fingerprint Signatures of Proteins and Mammalian Cells
Binding energies of tyrosine kinase inhibitors: Error assessment of computational methods for imatinib and nilotinib binding
Biomimetic whitlockite inorganic nanoparticles-mediated in situ remodeling and rapid bone regeneration
Determination of effective charges and ionic mobilities of polycationic antimicrobial peptides by capillary isotachophoresis and capillary zone electrophoresis
Water-soluble molecularly imprinted nanoparticles (MINPs) with tailored, functionalized, modifiable binding pockets
Water-Soluble Molecularly Imprinted Nanoparticles (MINPs) with Tailored, Functionalized, Modifiable Binding Pockets
Protein charge ladders reveal that the net charge of ALS-linked superoxide dismutase can be different in sign and magnitude from predicted values
Statins in therapy: understanding their hydrophilicity, lipophilicity, binding to 3-hydroxy-3-methylglutaryl-CoA reductase, ability to cross the blood brain barrier and metabolic stability based on electrostatic molecular orbital studies
Laboratory Evolution of Bacillus circulans Xylanase Inserted into Pyrococcus furiosus Maltodextrin-Binding Protein for Increased Xylanase Activity and Thermal Stability Toward Alkaline pH
Lysine acylation in superoxide dismutase-1 electrostatically inhibits formation of fibrils with prion-like seeding
Comprehensive genomic analysis of the CNGC gene family in Brassica oleracea: novel insights into synteny, structures, and transcript profiles
Human muscle-specific A-kinase anchoring protein polymorphisms modulate the susceptibility to cardiovascular diseases by altering cAMP/PKA signaling
Determination of the microenvironment-pH and charge and size characteristics of amino acids through their electrophoretic mobilities determined by CZE
Electrostatic charging due to separation of ions at interfaces: contact electrification of ionic electrets
Lysine acetylation can generate highly charged enzymes with increased resistance toward irreversible inactivation
Measurement of the differences in electrophoretic mobilities of individual molecules of E. coli beta-galactosidase provides insight into structural differences which underlie enzyme microheterogeneity
Genetic and chemical approaches for surface charge engineering of enzymes and their applicability in biocatalysis: A review
Hydrodynamic and Electrophoretic Properties of Trastuzumab/HER2 Extracellular Domain Complexes as Revealed by Experimental Techniques and Computational Simulations
The Early Phase of β2m Aggregation: An Integrative Computational Study Framed on the D76N Mutant and the ΔN6 Variant
Mesoporous silica particles as potential carriers for protein drug delivery: protein immobilization and the effect of displacer on γ-globulin release
Scaling form of viscosity at all length-scales in poly(ethylene glycol) solutions studied by fluorescence correlation spectroscopy and capillary electrophoresis
Reduced net charge and heterogeneity of pI isoforms in familial amyotrophic lateral sclerosis mutants of copper/zinc superoxide dismutase
Structure and effective charge characterization of proteins by a mobility capillary electrophoresis based method
2D square arrays of protein nanocages through channel-directed electrostatic interactions with poly(α, l-lysine)
Anomalous multipole expansion: Charge regulation of patchy inhomogeneously charged spherical particles
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