|dc.contributor.author||Kee Nyung Lee||-|
|dc.contributor.author||Ha Na Im||-|
|dc.contributor.author||Sang Won Kang||-|
|dc.contributor.author||Myeong Hee Yu||-|
|dc.description.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.||-|
|dc.publisher||Amer Soc Biochemistry Molecular Biology Inc||-|
|dc.title||Characterization of a human α₁-antitrypsin variant that is as stable as ovalbumin||-|
|dc.title.alternative||Characterization of a human α₁-antitrypsin variant that is as stable as ovalbumin||-|
|dc.citation.title||Journal of Biological Chemistry||-|
|dc.identifier.bibliographicCitation||Journal of Biological Chemistry, vol. 273, no. 5, pp. 2509-2516||-|
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