H/D Exchange Characterization of Silent Coupling: Entropy-Enthalpy Compensation in Allostery.

ABSTRACT: The allosteric coupling constant in K-type allosteric systems is defined as a ratio of the binding of substrate in the absence of effector to the binding of the substrate in the presence of a saturating concentration of effector. As a result, the coupling constant is itself an equilibrium value comprised of a ΔH and a TΔS component. In the scenario in which TΔS completely compensates ΔH, no allosteric influence of effector binding on substrate affinity is observed. However, in this "silent coupling" scenario, the presence of effector causes a change in the ΔH associated with substrate binding. A suggestion has now been made that "silent modulators" are ideal drug leads because they can be modified to act as either allosteric activators or inhibitors. Any attempt to rationally design the ef

SUBMITTER: Prasannan CB 

PROVIDER: S-EPMC7300342 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature