Transporter-to-trap conversion: a disulfide bond formation in cellular retinoic acid binding protein I mutant triggered by retinoic acid binding irreversibly locks the ligand inside the protein.

ABSTRACT: Transport proteins must bind their ligands reversibly to enable release at the point of delivery, while irreversible binding is usually associated with the extreme cases of ligand sequestration. Protein conformational dynamics is an important modulator of binding kinetics, as increased flexibility in the regions adjacent to the binding site may facilitate both association and dissociation processes. Ligand entry to, and exit from, the internal binding site of the cellular retinoic acid binding protein I (CRABP I) occurs via a flexible portal region, which functions as a dynamic aperture. We designed and expressed a CRABP I mutant (A35C/T57C), in which a small-scale conformational switch caused by the ligand binding event triggers formation of a disulfide bond in the portal region, thereby

SUBMITTER: Sjoelund V 

PROVIDER: S-EPMC2519245 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature