TY - JOUR

T1 - Investigation of DMSO-induced conformational transitions in human serum albumin using two-dimensional Raman optical activity spectroscopy

AU - Batista, Andrea N. L.

AU - Batista, Joao M.

AU - Ashton, Lorna

AU - Bolzani, Vanderlan S.

AU - Furlan, Maysa

AU - Blanch, Ewan W.

PY - 2014/9

Y1 - 2014/9

N2 - Recent Raman and Raman optical activity (ROA) results have demonstrated that dimethyl sulfoxide (DMSO) induces the selective conversion of alpha-helix motifs into the poly(L-proline) II (PPII) helix conformation in an array of proteins, while beta-sheets remain mostly unaffected. Human serum albumin (HSA), a highly alpha-helical protein, underwent the most dramatic changes and, therefore, was selected as a model for further investigations into the mechanism of this conformational change. Herein we report the use of two-dimensional ROA correlation analysis applying synchronous, autocorrelation, and moving windows approaches in order to understand the conformational transitions in HSA as a function of DMSO concentration. Our results indicate that the destabilization of native alpha-helix starts at DMSO concentrations as little as 20% in water (v/v), with the transition to PPII helix being complete at similar to 80% DMSO. These results clearly indicate that any protein preparation containing relatively low concentrations of DMSO should consider possible disruptions in alpha-helical domains. (C) 2014 Wiley Periodicals, Inc.

AB - Recent Raman and Raman optical activity (ROA) results have demonstrated that dimethyl sulfoxide (DMSO) induces the selective conversion of alpha-helix motifs into the poly(L-proline) II (PPII) helix conformation in an array of proteins, while beta-sheets remain mostly unaffected. Human serum albumin (HSA), a highly alpha-helical protein, underwent the most dramatic changes and, therefore, was selected as a model for further investigations into the mechanism of this conformational change. Herein we report the use of two-dimensional ROA correlation analysis applying synchronous, autocorrelation, and moving windows approaches in order to understand the conformational transitions in HSA as a function of DMSO concentration. Our results indicate that the destabilization of native alpha-helix starts at DMSO concentrations as little as 20% in water (v/v), with the transition to PPII helix being complete at similar to 80% DMSO. These results clearly indicate that any protein preparation containing relatively low concentrations of DMSO should consider possible disruptions in alpha-helical domains. (C) 2014 Wiley Periodicals, Inc.

KW - ROA

KW - 2DCOS

KW - HSA

KW - moving windows

KW - protein

KW - secondary structure

KW - PPII helix

KW - BOVINE ALPHA-LACTALBUMIN

KW - SEQUENTIAL ORDER

KW - PROTEINS

KW - HELIX

KW - LYSOZYME

KW - RULES

KW - STATE

U2 - 10.1002/chir.22351

DO - 10.1002/chir.22351

M3 - Journal article

VL - 26

SP - 497

EP - 501

JO - Chirality

JF - Chirality

SN - 0899-0042

IS - 9

ER -