Ligand binding remodels protein side-chain conformational heterogeneity.

ABSTRACT: While protein conformational heterogeneity plays an important role in many aspects of biological function, including ligand binding, its impact has been difficult to quantify. Macromolecular X-ray diffraction is commonly interpreted with a static structure, but it can provide information on both the anharmonic and harmonic contributions to conformational heterogeneity. Here, through multiconformer modeling of time- and space-averaged electron density, we measure conformational heterogeneity of 743 stringently matched pairs of crystallographic datasets that reflect unbound/apo and ligand-bound/holo states. When comparing the conformational heterogeneity of side chains, we observe that when binding site residues become more rigid upon ligand binding, distant residues tend to become more flex

SUBMITTER: Wankowicz SA 

PROVIDER: S-EPMC9084896 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature