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==Substituted 2-Naphthamidine Inhibitors of Urokinase==
==Substituted 2-Naphthamidine Inhibitors of Urokinase==
<StructureSection load='1owh' size='340' side='right' caption='[[1owh]], [[Resolution|resolution]] 1.61&Aring;' scene=''>
<StructureSection load='1owh' size='340' side='right'caption='[[1owh]], [[Resolution|resolution]] 1.61&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1owh]] is a 1 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=1OWH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OWH FirstGlance]. <br>
<table><tr><td colspan='2'>[[1owh]] is a 1 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=1OWH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OWH FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=239:6-[(Z)-AMINO(IMINO)METHYL]-N-[4-(AMINOMETHYL)PHENYL]-2-NAPHTHAMIDE'>239</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.61&#8491;</td></tr>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fv9|1fv9]], [[1owd|1owd]], [[1owe|1owe]], [[1owi|1owi]], [[1owj|1owj]], [[1owk|1owk]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=239:6-[(Z)-AMINO(IMINO)METHYL]-N-[4-(AMINOMETHYL)PHENYL]-2-NAPHTHAMIDE'>239</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr><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 Homo sapiens])</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=1owh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1owh OCA], [https://pdbe.org/1owh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1owh RCSB], [https://www.ebi.ac.uk/pdbsum/1owh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1owh ProSAT]</span></td></tr>
<tr><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>
</table>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1owh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1owh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1owh RCSB], [http://www.ebi.ac.uk/pdbsum/1owh PDBsum]</span></td></tr>
<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/ow/1owh_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ow/1owh_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=1owh 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 1owh" 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: Geyer, A.]]
[[Category: Geyer A]]
[[Category: Giranda, V L.]]
[[Category: Giranda VL]]
[[Category: Klinghofer, V.]]
[[Category: Klinghofer V]]
[[Category: Mantei, R.]]
[[Category: Mantei R]]
[[Category: McClellan, W.]]
[[Category: McClellan W]]
[[Category: Nienaber, V L.]]
[[Category: Nienaber VL]]
[[Category: Rockway, T W.]]
[[Category: Rockway TW]]
[[Category: Stewart, K.]]
[[Category: Stewart K]]
[[Category: Weitzberg, M.]]
[[Category: Weitzberg M]]
[[Category: Wendt, M D.]]
[[Category: Wendt MD]]
[[Category: Zhao, X.]]
[[Category: Zhao X]]
[[Category: Egf-like domain]]
[[Category: Glycoprotein]]
[[Category: Hydrolase]]
[[Category: Kringle]]
[[Category: Plasminogen activation]]
[[Category: Serine protease]]

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OCA