Conformation changes of albumin in its interaction with physiologically active compounds as studied by quasi-elastic light scattering spectroscopy and ultrasonic method

The effect of pH and binding of ten physiologically active compounds (PAC) on conformational organization of human serum albumin (HSA) in aqueous solutions has been studied using two different methods. The hydrodynamic sizes of albumin globule and its subunits were obtained from diffusion coefficients measured by quasi-elastic light scattering. The adiabatic volume compressibility of albumin was evaluated from ultrasonic velocity and density measurements. It was found, that albumin globule has the most compact configuration (hydrodynamic diameter 59-62 A and molar compressibility 5.6 m(3) Pa(-1) mol(-1)) at physiological pH 7.4. The changes in pH, both increase to 8.0 and decrease to 5.4, result in the growth of globule size to 68-81 A. An additional peak corresponding to diffusion of the separate albumin subdomains (hydrodynamic diameter 32-40 A) is observed in the light scattering spectra and globule compressibility decrease to 4.5-2.8 m(3) Pa(-1) mol(-1) at the acidic shift of pH. The additional peak was not displayed and globule compressibility increased to 6.4 m(3) Pa(-1) mol(-1) at the basic shift of pH. The acidic changes were attributed to unfolded and elastic conformation of albumin with a high motility of separate subdomains, whilst the basic changes correspond to a closed compressible configuration of albumin molecule. The interaction with propranolol, clonidine, phenylephrine, carbachol and tripeptide fMLP, which hinder adenylate cyclase (AdC) and activate Ca-polyphosphoinisitide (Ca-PPI) signaling system of a cell, initiates structural rearrangements similar to acidic transitions of albumin. Isoproterenol, yohimbine, diphenhydramine, chlorpromazine and atropine, which activate AdC and hinder Ca-PPI, cause conformational changes of albumin similar to basic transitions. The results obtained are consistent with the idea of structural and pharmacological similarity among the drugs inside the marked groups.