کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2184684 1095913 2012 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Enthalpy–Entropy Compensation and Cooperativity as Thermodynamic Epiphenomena of Structural Flexibility in Ligand–Receptor Interactions
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Enthalpy–Entropy Compensation and Cooperativity as Thermodynamic Epiphenomena of Structural Flexibility in Ligand–Receptor Interactions
چکیده انگلیسی

Ligand binding is a thermodynamically cooperative process in many biochemical systems characterized by the conformational flexibility of the reactants. However, the contribution of conformational entropy to cooperativity of ligation needs to be elucidated. Here, we perform kinetic and thermodynamic analyses on a panel of cycle-mutated peptides, derived from influenza H3 HA306–319, interacting with wild type and a mutant HLA-DR. We observe that, within a certain range of peptide affinity, this system shows isothermal entropy–enthalpy compensation (iEEC). The incremental increases in conformational entropy measured as disruptive mutations are added in the ligand or receptor are more than sufficient in magnitude to account for the experimentally observed lack of free-energy decrease cooperativity. Beyond this affinity range, compensation is not observed, and therefore, the ability of the residual interactions to form a stable complex decreases in an exponential fashion. Taken together, our results indicate that cooperativity and iEEC constitute the thermodynamic epiphenomena of the structural fluctuation that accompanies ligand–receptor complex formation in flexible systems. Therefore, ligand binding affinity prediction needs to consider how each source of binding energy contributes synergistically to the folding and kinetic stability of the complex in a process based on the trade-off between structural tightening and restraint of conformational mobility.

Graphical AbstractFigure optionsDownload high-quality image (81 K)Download as PowerPoint slideHighlights
► What is the contribution of conformational entropy to cooperativity CC of ligation?
► In flexible systems, disrupting interactions does not always translate to ΔG  CC.
► Entropy–enthalpy compensation is observed in the energetic range where CC is null/low.
► CC and iEEC constitute the opponent thermodynamic epiphenomena of a flexible system.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 417, Issue 5, 13 April 2012, Pages 454–467
نویسندگان
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