Unintended specificity of an engineered ligand-binding protein facilitated by unpredicted plasticity of the protein fold.

ABSTRACT: Attempts to create novel ligand-binding proteins often focus on formation of a binding pocket with shape complementarity against the desired ligand (particularly for compounds that lack distinct polar moieties). Although designed proteins often exhibit binding of the desired ligand, in some cases they display unintended recognition behavior. One such designed protein, that was originally intended to bind tetrahydrocannabinol (THC), was found instead to display binding of 25-hydroxy-cholecalciferol (25-D3) and was subjected to biochemical characterization, further selections for enhanced 25-D3 binding affinity and crystallographic analyses. The deviation in specificity is due in part to unexpected altertion of its conformation, corresponding to a significant change of the orientation of an

SUBMITTER: Day AL 

PROVIDER: S-EPMC6692866 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature