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

L Mølgaard, C P Ponting, U Christensen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)363-8
Number of pages6
JournalFEBS Letters
Volume405
Issue number3
Publication statusPublished - 1 Apr 1997

Keywords

  • Asparagine
  • Glycoproteins
  • Glycosylation
  • Humans
  • Kinetics
  • Ligands
  • Plasminogen
  • Protein Conformation
  • Spectrometry, Fluorescence
  • Tranexamic Acid

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