1o5b: Difference between revisions

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==Dissecting and Designing Inhibitor Selectivity Determinants at the S1 site Using an Artificial Ala190 Protease (Ala190 uPA)==
==Dissecting and Designing Inhibitor Selectivity Determinants at the S1 site Using an Artificial Ala190 Protease (Ala190 uPA)==
<StructureSection load='1o5b' size='340' side='right' caption='[[1o5b]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
<StructureSection load='1o5b' size='340' side='right'caption='[[1o5b]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1o5b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O5B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1O5B FirstGlance]. <br>
<table><tr><td colspan='2'>[[1o5b]] 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=1O5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O5B FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=ESI:4-IODOBENZO[B]THIOPHENE-2-CARBOXAMIDINE'>ESI</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]] 1.85&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gjc|1gjc]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=ESI:4-IODOBENZO[B]THIOPHENE-2-CARBOXAMIDINE'>ESI</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLAU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1o5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o5b OCA], [https://pdbe.org/1o5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o5b RCSB], [https://www.ebi.ac.uk/pdbsum/1o5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o5b ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1o5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o5b OCA], [http://pdbe.org/1o5b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1o5b RCSB], [http://www.ebi.ac.uk/pdbsum/1o5b 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/o5/1o5b_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o5/1o5b_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=1o5b ConSurf].
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<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
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==See Also==
==See Also==
*[[Urokinase|Urokinase]]
*[[Urokinase 3D Structures|Urokinase 3D Structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: U-plasminogen activator]]
[[Category: Large Structures]]
[[Category: Chan, H]]
[[Category: Chan H]]
[[Category: Gjerstad, E]]
[[Category: Gjerstad E]]
[[Category: Ho, J D]]
[[Category: Ho JD]]
[[Category: Janc, J W]]
[[Category: Janc JW]]
[[Category: Katz, B A]]
[[Category: Katz BA]]
[[Category: Luong, C]]
[[Category: Luong C]]
[[Category: Mackman, R L]]
[[Category: Mackman RL]]
[[Category: McGrath, M E]]
[[Category: McGrath ME]]
[[Category: Mortara, K]]
[[Category: Mortara K]]
[[Category: Somoza, J R]]
[[Category: Somoza JR]]
[[Category: Sprengeler, P A]]
[[Category: Sprengeler PA]]
[[Category: Tang, J]]
[[Category: Tang J]]
[[Category: Verner, E]]
[[Category: Verner E]]
[[Category: Williams, S R]]
[[Category: Williams SR]]
[[Category: Young, W B]]
[[Category: Young WB]]
[[Category: Ala190 upa]]
[[Category: Blood clotting]]
[[Category: Conserved water displacement hydrogen bond deficit]]
[[Category: Factor viia]]
[[Category: Hepsin]]
[[Category: Hydrolase]]
[[Category: S1 site]]
[[Category: Selectivity]]
[[Category: Thrombin]]
[[Category: Trypsin]]

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