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Analysis of the plasma elimination kinetics and conformational stabilities of native, proteinase-complexed, and reactive site cleaved serpins: comparison of alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, antithrombin III, alpha 2-antiplasmin, angiotensinogen, and ovalbumin.

Publication ,  Journal Article
Mast, AE; Enghild, JJ; Pizzo, SV; Salvesen, G
Published in: Biochemistry
February 12, 1991

Proteinase inhibitors of the serpin superfamily may exist in one of three distinct conformations: the native form, a fully active protein with the reactive site loop intact; the proteolytically modified form in which inhibitory capacity is abolished; and the proteinase-complexed form, a stable equimolar complex between the inhibitor and a target proteinase. Here, the specificity and kinetics of the plasma elimination of different serpin conformations are compared. Proteinase-complexed serpins were rapidly cleared from the circulation. However, the native and modified forms were not cleared rapidly, indicating that the receptor-mediated pathways which recognize the complexes fail to recognize the native and modified forms. This result suggests that significant structural differences exist between modified and proteinase-complexed serpins. The structural differences were probed by using transverse urea gradient gel electrophoresis, a technique that allows comparisons of the conformational stabilities of proteins. With the exception of the noninhibitory serpins ovalbumin and angiotensinogen, the modified and proteinase-complexed serpins were both stabilized thermodynamically compared to the native forms. In addition, the proteinase component of the serpin-proteinase complex was usually thermodynamically stabilized. These data are used to compare the conformations of serpin-proteinase complexes with those of native and modified serpins; they are discussed in terms of a model whereby serpins inhibit proteinases in a manner similar to that described for other types of protein inhibitors of serine proteinases.

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Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

February 12, 1991

Volume

30

Issue

6

Start / End Page

1723 / 1730

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • alpha 1-Antitrypsin
  • alpha 1-Antichymotrypsin
  • Serpins
  • Serine Endopeptidases
  • Sequence Homology, Nucleic Acid
  • Protein Conformation
  • Protein Binding
  • Ovalbumin
  • Molecular Sequence Data
 

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Journal cover image

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

February 12, 1991

Volume

30

Issue

6

Start / End Page

1723 / 1730

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • alpha 1-Antitrypsin
  • alpha 1-Antichymotrypsin
  • Serpins
  • Serine Endopeptidases
  • Sequence Homology, Nucleic Acid
  • Protein Conformation
  • Protein Binding
  • Ovalbumin
  • Molecular Sequence Data