1BUI

Structure of the ternary microplasmin-staphylokinase-microplasmin complex: a proteinase-cofactor-substrate complex in action

Summary for 1BUI

• Entry DOI: 10.2210/pdb1bui/pdb
• Related PRD ID: PRD_000288
• Descriptor: Plasminogen, Staphylokinase, L-alpha-glutamyl-N-{(1S)-4-{[amino(iminio)methyl]amino}-1-[(1S)-2-chloro-1-hydroxyethyl]butyl}glycinamide, ... (4 entities in total)
• Functional Keywords: plasmin, staphylokinase, serine proteinase, fibrinolysis, cofactor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted : P00747 P15240
• Total number of polymer chains: 3
• Total formula weight: 69665.31

Authors

Parry, M.A.A.,Fernandez-Catalan, C.,Bergner, A.,Huber, R.,Hopfner, K.,Schlott, B.,Guehrs, K.,Bode, W. (deposition date: 1998-09-04, release date: 1999-09-02, Last modification date: 2024-10-30)

Primary citation

Parry, M.A.,Fernandez-Catalan, C.,Bergner, A.,Huber, R.,Hopfner, K.P.,Schlott, B.,Guhrs, K.H.,Bode, W.
The ternary microplasmin-staphylokinase-microplasmin complex is a proteinase-cofactor-substrate complex in action.
Nat.Struct.Biol., 5:917-923, 1998

PubMed Abstract: The serine proteinase plasmin is the key fibrinolytic enzyme that dissolves blood clots and also promotes cell migration and tissue remodeling. Here, we report the 2.65 A crystal structure of a ternary complex of microplasmin-staphylokinase bound to a second microplasmin. The staphylokinase 'cofactor' does not affect the active-site geometry of the plasmin 'enzyme', but instead modifies its subsite specificity by providing additional docking sites for enhanced presentation of the plasminogen 'substrate' to the 'enzymes's' active site. The activation loop of the plasmin 'substrate', cleaved in these crystals, can be reconstructed to show how it runs across the active site of the plasmin 'enzyme' prior to activation cleavage. This is the first experimental structure of a productive proteinase-cofactor-macromolecular substrate complex. Furthermore, it provides a template for the design of improved plasminogen activators and plasmin inhibitors with considerable therapeutical potential.

PubMed: 9783753
DOI: 10.1038/2359

Experimental method

X-RAY DIFFRACTION (2.65 Å)