title: Kinetic and Thermodynamic Evaluation of Kynurenic Acid Binding to GluR1270-300 Polypeptide by Surface Plasmon Resonance Experiments.
abstract: This work clearly demonstrates an evaluation process that is easily performed and is simply based on the fitting of temperature-dependent surface plasmon resonance (SPR) sensorgrams to provide detailed thermodynamic characterization of biologically relevant interactions. The reversible binding of kynurenic acid (KYNA) on human glutamate receptor (GluR1) polypeptide (GluR1270-300)-modified gold surface has been studied at various temperatures under physiological conditions by two-dimensional SPR experiments. The registered sensorgrams were fitted by using different kinetic models without application of any commercial software. Assuming that the association of GluR1270-300-KYNA complex is first order in both reactants, the association (ka) and dissociation (kd) constants as well as the equilibrium constants (KA) and the Gibbs free-energy change (ΔG°) were given at 10, 20, 30, and 40 °C. Moreover, the enthalpy (ΔH° = -27.91 kJ mol(-1)), entropy (ΔS° = -60.33 J mol(-1) K(-1)), and heat capacity changes (ΔCp = -1.28 kJ mol(-1) K(-1)) of the model receptor-ligand system were also calculated using a spreadsheet program. Negative values of ΔG° and ΔH° indicate the exothermic formation of a stable GluR1270-300-KYNA complex, because the |ΔH| > |TΔS| relation suggests an enthalpy-driven binding process. The negative ΔH° and ΔS° values strongly support the formation of a salt bridge between KYNA and the positively charged residues of the polypeptide (Arg, Lys) at pH 7.4, confirmed by molecular docking calculations as well.
authors.affiliation: MTA-SZTE Supramolecular and Nanostructured Materials Research Group and ‡Department of Medical Chemistry, Faculty of Medicine, University of Szeged , Dóm tér 8., Szeged H-6720, Hungary.|MTA-SZTE Neuroscience Research Group and ∥Department of Neurology, University of Szeged , Semmelweis u. 6, Szeged H-6725, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Juhász
authors.affiliation: MTA-SZTE Supramolecular and Nanostructured Materials Research Group and ‡Department of Medical Chemistry, Faculty of Medicine, University of Szeged , Dóm tér 8., Szeged H-6720, Hungary.|MTA-SZTE Neuroscience Research Group and ∥Department of Neurology, University of Szeged , Semmelweis u. 6, Szeged H-6725, Hungary.
authors.forename: Edit
authors.initials: E
authors.lastname: Csapó
authors.affiliation: MTA-SZTE Supramolecular and Nanostructured Materials Research Group and ‡Department of Medical Chemistry, Faculty of Medicine, University of Szeged , Dóm tér 8., Szeged H-6720, Hungary.|MTA-SZTE Neuroscience Research Group and ∥Department of Neurology, University of Szeged , Semmelweis u. 6, Szeged H-6725, Hungary.
authors.forename: Ditta
authors.initials: D
authors.lastname: Ungor
authors.affiliation: MTA-SZTE Supramolecular and Nanostructured Materials Research Group and ‡Department of Medical Chemistry, Faculty of Medicine, University of Szeged , Dóm tér 8., Szeged H-6720, Hungary.|MTA-SZTE Neuroscience Research Group and ∥Department of Neurology, University of Szeged , Semmelweis u. 6, Szeged H-6725, Hungary.
authors.forename: Gábor K
authors.initials: GK
authors.lastname: Tóth
authors.affiliation: MTA-SZTE Supramolecular and Nanostructured Materials Research Group and ‡Department of Medical Chemistry, Faculty of Medicine, University of Szeged , Dóm tér 8., Szeged H-6720, Hungary.|MTA-SZTE Neuroscience Research Group and ∥Department of Neurology, University of Szeged , Semmelweis u. 6, Szeged H-6725, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.affiliation: MTA-SZTE Supramolecular and Nanostructured Materials Research Group and ‡Department of Medical Chemistry, Faculty of Medicine, University of Szeged , Dóm tér 8., Szeged H-6720, Hungary.|MTA-SZTE Neuroscience Research Group and ∥Department of Neurology, University of Szeged , Semmelweis u. 6, Szeged H-6725, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Dékány
mesh_terms: D006046:Gold; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D007736:Kynurenic Acid / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D013816:Thermodynamics
chemical_list: D006046:Gold; D007736:Kynurenic Acid; D018091:Receptors, AMPA