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 solu tions has been studied using two different methods. The hydrodynamic sizes of albumin globule and its subunits were obtained from diffusion coefficien ts measured by quasi-elastic light scattering. The adiabatic volume compres sibility of albumin was evaluated from ultrasonic velocity and density meas urements. It was found, that albumin globule has the most compact configura tion (hydrodynamic diameter 59-62 Angstrom 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 ngstrom. An additional peak corresponding to diffusion of the separate albu min subdomains (hydrodynamic diameter 32-40 Angstrom) is observed in the li ght 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 displa yed and globule compressibility increased to 6.4 m(3) Pa-1 mol(-1) at the b asic shift of pH. The acidic changes were attributed to unfolded and elasti c conformation of albumin with a high motility of separate subdomains, whil st the basic changes correspond to a closed compressible configuration of a lbumin molecule. The interaction with propranolol, clonidine, phenylephrine , carbachol and tripeptide fMLP, which hinder adenylate cyclase (AdC) and a ctivate Ca-polyphosphoinisitide (Ca-PPI) signaling system of a cell, initia tes structural rearrangements similar to acidic transitions of albumin. Iso proterenol, yohimbine, diphenhydramine, chlorpromazine and atropine, which activate AdC and hinder Ca-PPI, cause conformational changes of albumin sim ilar to basic transitions. The results obtained are consistent with the ide a of structural and pharmacological similarity among the drugs inside the m arked groups. (C) 2000 Elsevier Science B.V. All rights reserved.