Glycosylation at Asn-289 facilitates the ligand-induced conformational changes of human Glu-plasminogen

FEBS Lett. 1997 Apr 1;405(3):363-8. doi: 10.1016/s0014-5793(97)00221-4.

Abstract

Glu-plasminogen exists in two major glycoforms (I and II). Glycoform I contains carbohydrate chains linked to Asn-289 and Thr-346, whereas glycoform II is glycosylated only at Thr-346. Disparities in carbohydrate content lead to differences in the important functional properties of the zymogen, e.g. the kinetics of activation. The kinetics of the large ligand-induced conformational changes of each of the Glu-plasminogen glycoforms have been studied using stopped-flow fluorescence. The results are in accordance with a conformational change governed by positive co-operative binding at two weak lysine-binding sites. Additional glycosylation at Asn-289 in Glu-plasminogen I results in a two-fold increase in the overall dissociation constant of a ligand, trans-4-aminomethyl-cyclohexane carboxylic acid. This effect stems directly from the reaction step during which the conformational changes occur. This implies a higher population of Glu-plasminogen I in the open conformation even in the absence of ligands, and thus accounts for a higher rate of activation of Glu-plasminogen I, in comparison with Glu-plasminogen II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asparagine
  • Glycoproteins / chemistry
  • Glycoproteins / metabolism
  • Glycoproteins / ultrastructure
  • Glycosylation
  • Humans
  • Kinetics
  • Ligands
  • Plasminogen / chemistry*
  • Plasminogen / metabolism
  • Plasminogen / ultrastructure
  • Protein Conformation
  • Spectrometry, Fluorescence
  • Tranexamic Acid / chemistry

Substances

  • Glycoproteins
  • Ligands
  • Tranexamic Acid
  • Asparagine
  • Plasminogen