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A Recombinant Human ${\alpha}_1$-Antitrypsin Variant, $M_{malton}$, Undergoes a Spontaneous Conformational Conversion into a Latent Form  

Jung, Chan-Hun (Department of Molecular Biology, Sejong University)
Im, Hana (Department of Molecular Biology, Sejong University)
Publication Information
Journal of Microbiology / v.41, no.4, 2003 , pp. 335-339 More about this Journal
Abstract
Many genetic variants of ${\alpha}_1$-antitrypsin have been associated with early onset emphysema and liver cirrhosis. However, the detailed structural basis of pathogenic ${\alpha}_1$-antitrypsin molecules is rarely known. Here we found that a recombinant $M_{malton}$ variant (Phe52-deleted) lost inhibitory activity by spontaneous conformational conversion into a more stable, inactive form under physiological conditions. Biochemical and spectroscopic data suggested that the variant converts into a reactive center loop-inserted conformation, resembling the latent form of plasminogen activator inhibitor-1.
Keywords
antitrypsin; conformational change; latent form; serine protease inhibitors;
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