Detection of secondary binding sites in proteins using fragment screening.

ABSTRACT: Proteins need to be tightly regulated as they control biological processes in most normal cellular functions. The precise mechanisms of regulation are rarely completely understood but can involve binding of endogenous ligands and/or partner proteins at specific locations on a protein that can modulate function. Often, these additional secondary binding sites appear separate to the primary binding site, which, for example for an enzyme, may bind a substrate. In previous work, we have uncovered several examples in which secondary binding sites were discovered on proteins using fragment screening approaches. In each case, we were able to establish that the newly identified secondary binding site was biologically relevant as it was able to modulate function by the binding of a small molecule.

SUBMITTER: Ludlow RF 

PROVIDER: S-EPMC4703025 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature