Protein substrate conformation and proteolysis.

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Abstract
The digestion rate of serum albumin in the presence of small molecular ligands was studied. It was found that reversible interaction with a given ligand reduces the digestibility by all the proteolytic enzymes studied. This is the case even when a statistical average of one ligand molecule is bound by the protein. The results suggest that binding of the small molecule causes a conformation change which renders the protein molecule more resistant against proteolytic digestion, and that the transformation is not restricted to a localized area, but may involve the entire molecule. The decreased digestibility is assumed to result from stabilization of a particular conformation state by binding of the ligand molecule. This stabilization restricts the number of equilibrium conformation states available for the protein in the absence of ligand. Consequently, the frequency of occurrence of conformations which offer access to hydrolyzable bonds will also be decreased, with the result of an over-all decrease in the digestion rate. It is proposed that the efficiency of proteolytic attack depends on the ability of the substrate protein to oscillate between a variety of conformation states.