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Title 

Characterization of a human α₁-antitrypsin variant that is as stable as ovalbumin

Authors 

Kee Nyung LeeHa Na ImSang Won KangMyeong Hee Yu

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

1998

Citation 

Journal of Biological Chemistry, vol. 273, no. 5, pp. 2509-2516

Keywords 

alpha 1 antitrypsinovalbuminserine proteinase inhibitorpancreatic elastaseamino acid substitutioncomplex formationconformational transitionenzyme analysisnonhuman

Abstract 

The metastability of inhibitory serpins (serine proteinase inhibitors) is thought to play a key role in the facile conformational switch and the insertion of the reactive center loop into the central β-sheet, A-sheet, during the formation of a stable complex between a serpin and its target proteinase. We have examined the folding and inhibitory activity of a very stable variant of human α1-antitrypsin, a prototype inhibitory serpin. A combination of seven stabilizing single amino acid substitutions of α1- antitrypsin, designated Multi-7, increased the midpoint of the unfolding transition to almost that of ovalbumin, a non-inhibitory but more stable serpin. Compared with the wild-type α1-antitrypsin, Multi-7 retarded the opening of A-sheet significantly, as revealed by the retarded unfolding and latency conversion of the native state. Surprisingly, Multi-7 α1- antitrypsin could form a stable complex with a target elastase with the same kinetic parameters and the stoichiometry of inhibition as the wild type, indicating that enhanced A-sheet closure conferred by Multi-7 does not affect the complex formation. It may be that the stability increase of Multi-7 α1- antitrypsin is not sufficient to influence the rate of loop insertion during the complex formation.

ISSN 

0021-9258

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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