FEBS Letters | |
Glycosylation at Asn‐289 facilitates the ligand‐induced conformational changes of human Glu‐plasminogen | |
Mølgaard, Lone1  Ponting, Chris P3  Christensen, Ulla2  | |
[1] Biologics Development, Novo Nordisk A/S, Hagedornsvej 1, DK-2820 Gentofte, Denmark;Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen, Denmark;University of Oxford, Fibrinolysis Research Unit, The Old Observatory, South Parks Road, Oxford OX1 3RH, United Kingdom | |
关键词: Glu-plasminogen; conformation of; Glu-plasminogen; glycoforms; Lysine binding site; AH site; Stopped-flow kinetics; Fibrinolysis; regulation of; 6-AHA; 6-aminohexanoic acid; t-AMCHA; trans-4-aminomethyl-cyclohexane carboxylic acid; LBS; lysine binding site; K1–K5; kringle-domains of Glu-plasminogen; AH ligand; amino hexyl ligand; α2PI; α2-proteinase inhibitor; AH site; amino hexyl site as defined in [17]; | |
DOI : 10.1016/S0014-5793(97)00221-4 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
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.
【 授权许可】
Unknown
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