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Title: Arginine 719 in human plasminogen mediates formation of the staphylokinase:plasmin activator complex
Authors: Jespers, L ×
Van Herzeele, N
Lijnen, Roger
Van Hoef, Bertha
De Maeyer, Marc
Collen, Desire
Lasters, I #
Issue Date: May-1998
Series Title: Biochemistry vol:37 issue:18 pages:6380-6
Abstract: Staphylokinase (Sak), a 16-kDa bacterial protein, forms a 1:1 stoichiometric complex with the serine proteinase domain of human plasmin, which in turn converts other plasminogen molecules into plasmin. To identify amino acid residues critical for generating the Sak:plasmin activator complex, alanine-scanning mutagenesis was performed on phage-displayed micro-plasminogen (microPlg). Substitution of Arg719 with Ala [microPlg(R719A)] disrupted complex formation, although the sensitivity of phage-displayed microPlg(R719A) to activation by urokinase and the amidolytic activity of the micro-plasmin derivative [microPli(R719A)] remained unaffected. Likewise, the soluble microPlg(R719A) molecule did not generate a functional activator complex with Sak, whereas quantitative activation into plasmin was obtained upon incubation with either urokinase or the Sak:plasmin complex. Real-time biospecific affinity measurements revealed that the Arg --> Ala substitution at position 719 increased the equilibrium dissociation constant between microPlg(R719A) and Sak from 46 nM to 1 microM, primarily by reducing the association rate constant. Arg719 has recently also been implied in the functional complex formation between human plasmin and streptokinase [Dawson, K. M., Marshall, J. M., Raper, R. H., Gilbert, R. J., and Ponting, C. P. (1994) Biochemistry 33, 12042-12047.], suggesting that both bacterial cofactors may share common structural and/or mechanistic aspects for plasminogen activation.
URI: 
ISSN: 0006-2960
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Biochemistry, Molecular and Structural Biology Section
× corresponding author
# (joint) last author

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