The ternary microplasmin–staphylokinase–microplasmin complex is a proteinase–cofactor–substrate complex in action
| Autor: | Marina A. A. Parry, Wolfram Bode, Robert Huber, Bernhard Schlott, Andreas Bergner, Carlos Fernandez-Catalan, Karl-Heinz Gührs, Karl-Peter Hopfner |
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| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular Macromolecular Substances Protein Conformation Plasmin Molecular Sequence Data Crystallography X-Ray Biochemistry Catalysis Substrate Specificity Serine Structural Biology Genetics medicine Humans Amino Acid Sequence Fibrinolysin Binding site Ternary complex chemistry.chemical_classification Binding Sites biology Metalloendopeptidases Active site Staphylokinase Peptide Fragments Enzyme chemistry Docking (molecular) biology.protein Sequence Alignment medicine.drug |
| Zdroj: | Nature Structural Biology. 5:917-923 |
| ISSN: | 1072-8368 |
| DOI: | 10.1038/2359 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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