Spectroscopic Studies on the Molecular Ageing of Serum Albumin.

Mariola Chudzik,Małgorzata Maciążek-Jurczyk,Anna Sułkowska,Bartosz Pawełczak

doi:10.3390/molecules22010034

Mariola Chudzik, Małgorzata Maciążek-Jurczyk + Show 2 more

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https://doi.org/10.3390/molecules22010034

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Journal: Molecules (Basel, Switzerland)	Publication Date: Dec 27, 2016
Citations: 29	License type: CC BY 4.0

Affiliation: Medical University of Silesia

Abstract

Pathological states in the organism, e.g., renal or hepatic diseases, cataract, dysfunction of coronary artery, diabetes mellitus, and also intensive workout, induce the structural modification of proteins called molecular ageing or N-A isomerization. The aim of this study was to analyze the structural changes of serum albumin caused by alkaline ageing using absorption, spectrofluorescence, and circular dichroism spectroscopy. The N-A isomerization generates significant changes in bovine (BSA) and human (HSA) serum albumin subdomains—the greatest changes were observed close to the tryptophanyl (Trp) and tyrosyl (Tyr) residue regions while a smaller change was observed in phenyloalanine (Phe) environment. Moreover, the changes in the polarity of the Trp neighborhood as well as the impact of the ageing process on α-helix, β-sheet content, and albumin molecule rotation degree have been analyzed. Based on the spectrofluorescence study, the alterations in metoprolol binding affinity to the specific sites that increase the toxicity of the drug were investigated.

Highlights

Serum albumin is the most important carrier protein for numerous endogenous and exogenous ligands [1]
582 amino acids, has two tryptophanyl residues
At the molar ratio of Human serum albumin (HSA) to both Dansyl glicyne (DG) and DP at 1:1, the displacement percentage of DG and DP was reduced to 27.9% and 33.29%, respectively (Table 4)

Summary

Introduction

Serum albumin is the most important carrier protein for numerous endogenous and exogenous ligands [1]. Human serum albumin (HSA), which contains 585 amino acids, has a single tryptophanyl residue (Trp214 located in subdomain IIA) while bovine serum albumin (BSA), which contains. 582 amino acids, has two tryptophanyl residues (Trp214 and Trp135 located in subdomains IIA and IB, respectively) [1,2]. The N(normal)-A(aged) isomerization leads to the structural relaxation of the protein structure. It mainly affects the N-terminal region and thereby may influence the ligand binding affinity [4,5]. The A(aged) form of bovine serum albumin (ABSA)

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