Interactions of Chlorpromazine with α-,β- and γ-Crystallins

Abstract

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 - α_L-crystallin, β_L-crystallin and γ-crystallin. The binding affinity constants for CPZ binding to α_L- and γ-crystallins are higher than the binding affinity constants for β_L-crystallin, although the number of CPZ binding sites for β_L-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 α_L-crystallin does not significantly alter the anti-aggregation properties of the molecular chaperone, α-crystallin against oxidation-induced aggregation of γ-crystallin at 37°C and thermal aggregation of alcohol dehydrogenase (ADH) at 48°C. Therefore, CPZ induced alteration in chaperone activity of α_L-crystallin is probably not associated with the formation of cataracts.