Stability of ligand-induced protein conformation influences affinity in maltose-binding protein

摘要: ABSTRACT Our understanding of what determines ligand affinity proteins is poor, even with high-resolution structures available. Both the non-covalent ligand-protein interactions and relative free energies available conformations contribute to a protein for ligand. Distant, non-binding site residues can influence by altering energy difference between ligand-free ligand-bound conformation. hypothesis that when different ligands induce distinct conformations, it should be possible tweak their affinities changing conformations. We tested this idea maltose-binding (MPB) from Escherichia coli. used singlemolecule Forster resonance transfer (smFRET) distinguish several unique MBP. engineered mutations, distant binding site, affect stabilities show indeed altered in conformation-dependent manner. studies provide framework tuning affinity, apart modifying residues.