Premium
Glycosylation at Asn‐289 facilitates the ligand‐induced conformational changes of human Glu‐plasminogen
Author(s) -
Mølgaard Lone,
Ponting Chris P,
Christensen Ulla
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00221-4
Subject(s) - chemistry , glycosylation , conformational change , biophysics , ligand (biochemistry) , biochemistry , receptor , biology
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.