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)
  • Published : 2003.01.01

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

References

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