Which Properties Allow Ligands to Open and Bind to the Transient Binding Pocket of Human Aldose Reductase?

ABSTRACT: The transient specificity pocket of aldose reductase only opens in response to specific ligands. This pocket may offer an advantage for the development of novel, more selective ligands for proteins with similar topology that lack such an adaptive pocket. Our aim was to elucidate which properties allow an inhibitor to bind in the specificity pocket. A series of inhibitors that share the same parent scaffold but differ in their attached aromatic substituents were screened using ITC and X-ray crystallography for their ability to occupy the pocket. Additionally, we investigated the electrostatic potentials and charge distribution across the attached terminal aromatic groups with respect to their potential to bind to the transient pocket of the enzyme using ESP calculations. These methods allow

SUBMITTER: Sandner A 

PROVIDER: S-EPMC8699021 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature