Influence of amino acids on alkaline pH induced partially folded molten globule like intermediate of bovine serum albumin: Conformational and thermodynamic insights

Abstract

Partially folded states of proteins can misfold or aggregate leading to various neurodegenerative diseases or disorders. Therefore stabilization of the partially folded states of proteins towards native conformation is important. Here, we investigate the effects of glycine, l-alanine, DL- α – aminobutyric acid, l-lysine, l-leucine and l-valine on the stability of molten globule like partially folded state of bovine serum albumin (BSA) at pH 11.2. We report the changes in the Trp microenvironment of the BSA at pH 11.2 by these amino acids. Except for l-leucine and l-valine, the other four amino acids impart thermal stabilization to partially folded MG like intermediate of BSA at pH 11.2. CD spectroscopy is employed to analyse tertiary conformation of BSA. We perform the ITC to study the interaction of BSA with these amino acids at pH 11.2. The spectroscopic in combination with calorimetric observations have enabled monitoring amino acid-induced conformational changes in BSA at pH 11.2 suggesting their osmolyte behavior. The results suggest significance of preferential hydration of partially folded proteins and the stability offered by the amino acids.