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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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1437-4315
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Volume 382, Issue 11

Issues

Osmolytes as Modulators of Conformational Changes in Serpins

Michelle K.M. Chow / Glyn L. Devlin / Stephen P. Bottomley
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2001.194

Abstract

Protein misfolding and aggregation play an integral role in many diseases. The misfolding of the serpin (SERine Proteinase INhibitor) α1-antitrypsin results in the accumulation of insoluble polymers within hepatocytes and α1-antitrypsin deficiency in plasma, predisposing patients to liver cirrhosis and emphysema. We have examined the effect of three naturally occurring osmolytes, sarcosine, glycine betaine and trimethylamine Noxide, on conformational changes in α1-antitrypsin. All three solutes protected native α1-antitrypsin against thermally induced polymerisation and inactivation in a concentrationdependent manner. Further spectroscopic analysis showed that sarcosine stabilises the native conformation of α1-antitrypsin, thus hindering its conversion to an intermediate state and subsequent polymerisation. On refolding in the presence of sarcosine, α1-antitrypsin formed a heterogeneous population, with increasing proportions of molecules adopting an inactive conformation in higher concentrations of the osmolyte. These data show that sarcosine can be used to prevent abnormal structural changes in native α1-antitrypsin, but is ineffective in facilitating the correct folding of the protein. The implications of these results in the context of conformational changes and states adopted by α1-antitrypsin are discussed.

About the article

Published Online: 2005-06-01

Published in Print: 2001-11-13


Citation Information: Biological Chemistry, Volume 382, Issue 11, Pages 1593–1599, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2001.194.

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