Interactions of chlorpromazine with alpha-, beta- and gamma-crystallins.

The binding parameters (binding affinity constant, K and number of binding sites, p) has been determined spectrofluorometrically for chlorpromazine (CPZ) binding to the lens proteins--alphaL-crystallin, betaL-crystallin and gamma-crystallin. The binding affinity constants for CPZ binding to alphaL- and gamma-crystallins are higher than the binding affinity constants for 3betaL-crystallin, although the number of CPZ binding sites for betaL-crystallin is comparatively higher than the number for the other two lens proteins. CPZ causes local conformational changes around the tryptophan moieties of the protein molecules but does not cause any gross conformational change within the protein moieties. Binding of CPZ to alphaL-crystallin does not significantly alter the anti-aggregation properties of the molecular chaperone, alphaL-crystallin against oxidation-induced aggregation of gamma-crystallin at 37 degrees C and thermal aggregation of alcohol dehydrogenase (ADH) at 48 degrees C. Therefore, CPZ induced alteration in chaperone activity of alphaL-crystallin is probably not associated with the formation of cataracts.