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The effect of substituted laminin A chain-derived peptides on the conformation and activation kinetics of plasminogen.

Publication ,  Journal Article
Stack, MS; Pizzo, SV
Published in: Arch Biochem Biophys
February 15, 1994

Conversion of the zymogen plasminogen (Pg) to the active enzyme plasmin is catalyzed by proteinases such as tissue-type plasminogen activator (t-PA). Interaction of Pg with small ligands such as lysine or macromolecular ligands such as fibrin induces a dramatic conformational change in the zymogen which enhances its efficacy as a t-PA substrate, thereby increasing catalytic efficiency of the activation reaction. We have previously demonstrated that a synthetic peptide derived from amino acids 2091-2108 of the laminin A chain (designated LamA2091-2108) can significantly enhance t-PA-catalyzed Pg activation. To probe the mechanism of this stimulatory reaction, we have determined the effect of substituted LamA2091-2108 derivatives on Pg activation by t-PA. Substitution of charged residues in LamA2091-2108 with neutral amino acids decreases the kcat/Km observed in the presence of native LamA2091-2108. Furthermore, fluorescence-quenching experiments demonstrate that whereas LamA2091-2108 alters the solvent accessibility of Pg Trp residues, charge-substituted peptides have little effect on Pg conformation. These data suggest that LamA2091-2108 stimulates Pg activation by inducing a conformational change in the zymogen similar to that observed upon binding of other ligands such as lysine and fibrin.

Duke Scholars

Published In

Arch Biochem Biophys

DOI

ISSN

0003-9861

Publication Date

February 15, 1994

Volume

309

Issue

1

Start / End Page

117 / 122

Location

United States

Related Subject Headings

  • Tissue Plasminogen Activator
  • Structure-Activity Relationship
  • Protein Conformation
  • Plasminogen
  • Peptide Fragments
  • Molecular Sequence Data
  • Laminin
  • Kinetics
  • Humans
  • Fibrinolysin
 

Citation

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Stack, M. S., & Pizzo, S. V. (1994). The effect of substituted laminin A chain-derived peptides on the conformation and activation kinetics of plasminogen. Arch Biochem Biophys, 309(1), 117–122. https://doi.org/10.1006/abbi.1994.1093
Stack, M. S., and S. V. Pizzo. “The effect of substituted laminin A chain-derived peptides on the conformation and activation kinetics of plasminogen.Arch Biochem Biophys 309, no. 1 (February 15, 1994): 117–22. https://doi.org/10.1006/abbi.1994.1093.
Stack, M. S., and S. V. Pizzo. “The effect of substituted laminin A chain-derived peptides on the conformation and activation kinetics of plasminogen.Arch Biochem Biophys, vol. 309, no. 1, Feb. 1994, pp. 117–22. Pubmed, doi:10.1006/abbi.1994.1093.
Journal cover image

Published In

Arch Biochem Biophys

DOI

ISSN

0003-9861

Publication Date

February 15, 1994

Volume

309

Issue

1

Start / End Page

117 / 122

Location

United States

Related Subject Headings

  • Tissue Plasminogen Activator
  • Structure-Activity Relationship
  • Protein Conformation
  • Plasminogen
  • Peptide Fragments
  • Molecular Sequence Data
  • Laminin
  • Kinetics
  • Humans
  • Fibrinolysin