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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Stack, MS; Pizzo, SV

Published Date

  • February 15, 1994

Published In

Volume / Issue

  • 309 / 1

Start / End Page

  • 117 - 122

PubMed ID

  • 8117101

International Standard Serial Number (ISSN)

  • 0003-9861

Digital Object Identifier (DOI)

  • 10.1006/abbi.1994.1093


  • eng

Conference Location

  • United States