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 language | English |
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Pages (from-to) | 363-8 |
Number of pages | 6 |
Journal | FEBS Letters |
Volume | 405 |
Issue number | 3 |
Publication status | Published - 1 Apr 1997 |
Keywords / Materials (for Non-textual outputs)
- Asparagine
- Glycoproteins
- Glycosylation
- Humans
- Kinetics
- Ligands
- Plasminogen
- Protein Conformation
- Spectrometry, Fluorescence
- Tranexamic Acid