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Biochem Biophys Res Commun. 1996 Sep 13;226(2):378-84.

Folding pathway of human alpha 1-antitrypsin: characterization of an intermediate that is active but prone to aggregation.

Author information

1
Division of Protein Engineering, Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea.

Abstract

The folding-unfolding kinetics of human alpha 1-antitrypsin (alpha 1-AT) were examined by monitoring intrinsic Trp fluorescence and extrinsic ANS fluorescence. While the unfolding of alpha 1-AT followed a single exponential phase, refolding exhibited three exponential phases. The fast phase (tau 1r < 40 sec). which was independent of urea concentration, appears to be hydrophobic collapse that may be limited by cis-trans isomerization of prolyl residue. The medium phase (tau 2s = 200 sec) yielded an intermediate (IN), which is capable of elastase binding. The slowest (tau 3r = 1000 sec) phase completes refolding to the native protein, which intersects with the unfolding kinetics at the same urea concentration (1.9 M) as the equilibrium midpoint. Concentration-dependence of the amplitude of major refolding phases indicated that IN is prone to kinetic competition between the on-pathway to native protein and aggregation.

PMID:
8806643
DOI:
10.1006/bbrc.1996.1364
[Indexed for MEDLINE]

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