Effects of ligand binding on the stability of aldo-keto reductases: Implications for stabilizer or destabilizer chaperones.

ABSTRACT: Ligands such as enzyme inhibitors stabilize the native conformation of a protein upon binding to the native state, but some compounds destabilize the native conformation upon binding to the non-native state. The former ligands are termed "stabilizer chaperones" and the latter ones "destabilizer chaperones." Because the stabilization effects are essential for the medical chaperone (MC) hypothesis, here we have formulated a thermodynamic system consisting of a ligand and a protein in its native- and non-native state. Using the differential scanning fluorimetry and the circular dichroism varying the urea concentration and temperature, we found that when the coenzyme NADP⁺ was absent, inhibitors such as isolithocholic acid stabilized the aldo-keto reductase AKR1A1 upon binding, whic

SUBMITTER: Kabir A 

PROVIDER: S-EPMC5119574 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature