Designing interactions by control of protein-ligand complex conformation: tuning arginine-arene interaction geometry for enhanced electrostatic protein-ligand interactions.

ABSTRACT: We investigated galectin-3 binding to 3-benzamido-2-O-sulfo-galactoside and -thiodigalactoside ligands using a combination of site-specific mutagenesis, X-ray crystallography, computational approaches, and binding thermodynamics measurements. The results reveal a conformational variability in a surface-exposed arginine (R144) side chain in response to different aromatic C3-substituents of bound galactoside-based ligands. Fluorinated C3-benzamido substituents induced a shift in the side-chain conformation of R144 to allow for an entropically favored electrostatic interaction between its guanidine group and the 2-O-sulfate of the ligand. By contrast, binding of ligands with non-fluorinated substituents did not trigger a conformational change of R144. Hence, a sulfate-arginine e

SUBMITTER: Noresson AL 

PROVIDER: S-EPMC5883865 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature