View source for 1sqt

==Substituted 2-Naphthamidine Inhibitors of Urokinase==
<StructureSection load='1sqt' size='340' side='right' caption='[[1sqt]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1sqt]] 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=1SQT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1SQT FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UI3:7-METHOXY-8-[1-(METHYLSULFONYL)-1H-PYRAZOL-4-YL]NAPHTHALENE-2-CARBOXIMIDAMIDE'>UI3</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1owd|1owd]], [[1owe|1owe]], [[1owh|1owh]], [[1owi|1owi]], [[1owj|1owj]], [[1owk|1owk]], [[1sqa|1sqa]], [[1sqo|1sqo]]</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><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sqt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sqt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1sqt RCSB], [http://www.ebi.ac.uk/pdbsum/1sqt PDBsum]</span></td></tr>
<table>
== 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>  
== Function ==
[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sq/1sqt_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Several 8-substituted 2-naphthamidine-based inhibitors of the serine protease urokinase plasminogen activator (uPA) are described. Direct attachment of five-membered saturated or unsaturated rings improved inhibitor performance; substitution with sulfones further improved binding profiles. Combination of these substituents or of previously described NH-linked heteroaromatic rings with 6-phenyl amide substituents provided further enhancements to potency and selectivity.

Interaction with the S1 beta-pocket of urokinase: 8-heterocycle substituted and 6,8-disubstituted 2-naphthamidine urokinase inhibitors.,Wendt MD, Geyer A, McClellan WJ, Rockway TW, Weitzberg M, Zhao X, Mantei R, Stewart K, Nienaber V, Klinghofer V, Giranda VL Bioorg Med Chem Lett. 2004 Jun 21;14(12):3063-8. PMID:15149645<ref>PMID:15149645</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>

==See Also==
*[[Urokinase|Urokinase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: U-plasminogen activator]]
[[Category: Geyer, A.]]
[[Category: Giranda, V L.]]
[[Category: Klinghofer, V.]]
[[Category: Mantei, R.]]
[[Category: McClellan, W J.]]
[[Category: Nienaber, V.]]
[[Category: Rockway, T W.]]
[[Category: Stewart, K.]]
[[Category: Weitzberg, M.]]
[[Category: Wendt, M D.]]
[[Category: Zhang, X.]]
[[Category: Egf-like domain]]
[[Category: Glycoprotein]]
[[Category: Hydrolase]]
[[Category: Kringle]]
[[Category: Plasminogen activation]]
[[Category: Serine protease]]