1bui
From Proteopedia
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==Overview== | ==Overview== | ||
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. | 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. | ||
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Conjunctivitis, ligneous OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173350 173350]], Plasminogen Tochigi disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173350 173350]], Plasminogen deficiency, types I and II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173350 173350]], Thrombophilia, dysplasminogenemic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173350 173350]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: staphylokinase]] | [[Category: staphylokinase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:14:38 2007'' |
Revision as of 14:08, 12 November 2007
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STRUCTURE OF THE TERNARY MICROPLASMIN-STAPHYLOKINASE-MICROPLASMIN COMPLEX: A PROTEINASE-COFACTOR-SUBSTRATE COMPLEX IN ACTION.
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Conjunctivitis, ligneous OMIM:[173350], Plasminogen Tochigi disease OMIM:[173350], Plasminogen deficiency, types I and II OMIM:[173350], Thrombophilia, dysplasminogenemic OMIM:[173350]
About this Structure
1BUI is a Protein complex structure of sequences from Homo sapiens. Active as Plasmin, with EC number 3.4.21.7 Structure known Active Sites: ASA and ASB. Full crystallographic information is available from OCA.
Reference
The ternary microplasmin-staphylokinase-microplasmin complex is a proteinase-cofactor-substrate complex in action., Parry MA, Fernandez-Catalan C, Bergner A, Huber R, Hopfner KP, Schlott B, Guhrs KH, Bode W, Nat Struct Biol. 1998 Oct;5(10):917-23. PMID:9783753
Page seeded by OCA on Mon Nov 12 16:14:38 2007
