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==ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OF SER190 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS==
==ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OF SER190 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS==
<StructureSection load='1gjb' size='340' side='right' caption='[[1gjb]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
<StructureSection load='1gjb' size='340' side='right'caption='[[1gjb]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1gjb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1GJB FirstGlance]. <br>
<table><tr><td colspan='2'>[[1gjb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GJB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GJB FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=130:2-(2-HYDROXY-BIPHENYL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE'>130</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</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]] 1.9&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c5x|1c5x]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=130:2-(2-HYDROXY-BIPHENYL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE'>130</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] </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=1gjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gjb OCA], [https://pdbe.org/1gjb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gjb RCSB], [https://www.ebi.ac.uk/pdbsum/1gjb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gjb ProSAT]</span></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=1gjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gjb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1gjb RCSB], [http://www.ebi.ac.uk/pdbsum/1gjb PDBsum]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[http://omim.org/entry/601709 601709]]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.<ref>PMID:20007542</ref>
[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[https://omim.org/entry/601709 601709]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.<ref>PMID:20007542</ref>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.  
[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
== 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/gj/1gjb_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gj/1gjb_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=1gjb 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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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 1gjb" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Urokinase|Urokinase]]
*[[Urokinase 3D Structures|Urokinase 3D Structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: U-plasminogen activator]]
[[Category: Large Structures]]
[[Category: Allen, D]]
[[Category: Allen D]]
[[Category: Breitenbucher, J G]]
[[Category: Breitenbucher JG]]
[[Category: Hui, H]]
[[Category: Hui H]]
[[Category: Katz, B A]]
[[Category: Katz BA]]
[[Category: Luong, C]]
[[Category: Luong C]]
[[Category: Mackman, R L]]
[[Category: Mackman RL]]
[[Category: Martelli, A]]
[[Category: Martelli A]]
[[Category: McGee, D]]
[[Category: McGee D]]
[[Category: Spencer, J R]]
[[Category: Spencer JR]]
[[Category: Sprengeler, P A]]
[[Category: Sprengeler PA]]
[[Category: Verner, E]]
[[Category: Verner E]]
[[Category: Blood clotting]]
[[Category: H2o displacement]]
[[Category: Hydrolase]]
[[Category: Selectivity at s1]]
[[Category: Ser190/ala190 protease]]
[[Category: Structure-based drug design]]
[[Category: Tpa]]
[[Category: Upa]]

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