Enthalpy-Entropy Compensation in the Binding of Modulators at Ionotropic Glutamate Receptor GluA2

Thermodynamics and structural analysis of positive allosteric modulation of the ionotropic glutamate receptor GluA2.

Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimer's disease. These modulators bind within the dimer interface of the LBD (ligand-binding domain) and stabilize the agonist-bound conformation slowing receptor desensitization and/or deactivation. In the present study, we employ isothermal t...

Enthalpy-entropy compensation at play in human copper ion transfer

Copper (Cu) is an essential trace element but toxic in free form. After cell uptake, Cu is transferred, via direct protein-protein interactions, from the chaperone Atox1 to the Wilson disease protein (WD) for incorporation into Cu-dependent enzymes. Cu binds to a conserved C(1)XXC(2) motif in the chaperone as well as in each of the cytoplasmic metal-binding domains of WD. Here, we dissect mecha...

A fundamental view of enthalpy–entropy compensation

Entropy-enthalpy compensation: fact or artifact?

The phenomenon of entropy-enthalpy (S-H) compensation is widely invoked as an explanatory principle in thermodynamic analyses of proteins, ligands, and nucleic acids. It has been suggested that this compensation is an intrinsic property of either complex, fluctuating, or aqueous systems. The questions examined here are whether the observed compensation is extra-thermodynamic (i.e., reflects any...

Molecular rigidity and enthalpy-entropy compensation in DNA melting.

Enthalpy-entropy compensation (EEC) is observed in diverse molecular binding processes of importance to living systems and manufacturing applications, but this widely occurring phenomenon is not sufficiently understood from a molecular physics standpoint. To gain insight into this fundamental problem, we focus on the melting of double-stranded DNA (dsDNA) since measurements exhibiting EEC are e...