Structure-based stabilization of insulin as a therapeutic protein assembly via enhanced aromatic-aromatic interactions.

ABSTRACT: Key contributions to protein structure and stability are provided by weakly polar interactions, which arise from asymmetric electronic distributions within amino acids and peptide bonds. Of particular interest are aromatic side chains whose directional π-systems commonly stabilize protein interiors and interfaces. Here, we consider aromatic-aromatic interactions within a model protein assembly: the dimer interface of insulin. Semi-classical simulations of aromatic-aromatic interactions at this interface suggested that substitution of residue Tyr^B26 by Trp would preserve native structure while enhancing dimerization (and hence hexamer stability). The crystal structure of a [Trp^B26]insulin analog (determined as a T₃R^f₃ zinc hexamer at a

SUBMITTER: Rege NK 

PROVIDER: S-EPMC6052209 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature