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==Structure of the ternary microplasmin-staphylokinase-microplasmin complex: a proteinase-cofactor-substrate complex in action==
==Structure of the ternary microplasmin-staphylokinase-microplasmin complex: a proteinase-cofactor-substrate complex in action==
<StructureSection load='1bui' size='340' side='right' caption='[[1bui]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
<StructureSection load='1bui' size='340' side='right'caption='[[1bui]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1bui]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bpp42 Bpp42] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BUI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BUI FirstGlance]. <br>
<table><tr><td colspan='2'>[[1bui]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_phage_42D.m Staphylococcus phage 42D.m]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BUI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BUI FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0GJ:L-ALPHA-GLUTAMYL-N-{(1S)-4-{[AMINO(IMINIO)METHYL]AMINO}-1-[(1S)-2-CHLORO-1-HYDROXYETHYL]BUTYL}GLYCINAMIDE'>0GJ</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Plasmin Plasmin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.7 3.4.21.7] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0GJ:L-ALPHA-GLUTAMYL-N-{(1S)-4-{[AMINO(IMINIO)METHYL]AMINO}-1-[(1S)-2-CHLORO-1-HYDROXYETHYL]BUTYL}GLYCINAMIDE'>0GJ</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bui OCA], [http://pdbe.org/1bui PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1bui RCSB], [http://www.ebi.ac.uk/pdbsum/1bui PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1bui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bui OCA], [https://pdbe.org/1bui PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bui RCSB], [https://www.ebi.ac.uk/pdbsum/1bui PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bui ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN]] Defects in PLG are the cause of plasminogen deficiency (PLGD) [MIM:[http://omim.org/entry/217090 217090]]. PLGD is characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.<ref>PMID:1986355</ref> <ref>PMID:8392398</ref> <ref>PMID:6216475</ref> <ref>PMID:6238949</ref> <ref>PMID:1427790</ref> <ref>PMID:9242524</ref> <ref>PMID:9858247</ref> <ref>PMID:10233898</ref>
[https://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN] Defects in PLG are the cause of plasminogen deficiency (PLGD) [MIM:[https://omim.org/entry/217090 217090]. PLGD is characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.<ref>PMID:1986355</ref> <ref>PMID:8392398</ref> <ref>PMID:6216475</ref> <ref>PMID:6238949</ref> <ref>PMID:1427790</ref> <ref>PMID:9242524</ref> <ref>PMID:9858247</ref> <ref>PMID:10233898</ref>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN]] Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.<ref>PMID:14699093</ref>  Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.<ref>PMID:14699093</ref> [[http://www.uniprot.org/uniprot/SAK_BPP42 SAK_BPP42]] Potent plasminogen activator that converts plasminogen into plasmin. It forms a 1:1 complex with plasmin, which in turn activates other plasminogen molecules.
[https://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN] Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.<ref>PMID:14699093</ref>  Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.<ref>PMID:14699093</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bu/1bui_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bu/1bui_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1bui ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
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==See Also==
==See Also==
*[[Plasminogen|Plasminogen]]
*[[Plasminogen 3D structures|Plasminogen 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bpp42]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Plasmin]]
[[Category: Staphylococcus phage 42D m]]
[[Category: Bergner, A]]
[[Category: Bergner A]]
[[Category: Bode, W]]
[[Category: Bode W]]
[[Category: Fernandez-Catalan, C]]
[[Category: Fernandez-Catalan C]]
[[Category: Guehrs, K]]
[[Category: Guehrs K]]
[[Category: Hopfner, K]]
[[Category: Hopfner K]]
[[Category: Huber, R]]
[[Category: Huber R]]
[[Category: Parry, M A.A]]
[[Category: Parry MAA]]
[[Category: Schlott, B]]
[[Category: Schlott B]]
[[Category: Cofactor]]
[[Category: Fibrinolysis]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Serine proteinase]]
[[Category: Staphylokinase]]

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