3ig6: Difference between revisions

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-{{Seed}}
+==Low molecular weigth human Urokinase type Plasminogen activator 2-[6-(3'-Aminomethyl-biphenyl-3-yloxy)-4-(3-dimethylamino-pyrrolidin-1-yl)-3,5-difluoro-pyridin-2-yloxy]-4-dimethylamino-benzoic acid complex==
-[[Image:3ig6.png|left|200px]]
+<StructureSection load='3ig6' size='340' side='right' caption='[[3ig6]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3ig6]] is a 4 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=3IG6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3IG6 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=438:2-[(6-{[3-(AMINOMETHYL)BIPHENYL-3-YL]OXY}-4-[(3R)-3-(DIMETHYLAMINO)PYRROLIDIN-1-YL]-3,5-DIFLUOROPYRIDIN-2-YL)OXY]-4-(DIMETHYLAMINO)BENZOIC+ACID'>438</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1sqa|1sqa]], [[1w14|1w14]], [[1vja|1vja]], [[1owj|1owj]], [[1f92|1f92]]</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='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=3ig6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ig6 OCA], [http://pdbe.org/3ig6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ig6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ig6 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/ig/3ig6_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/main_output.php?pdb_ID=3ig6 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+In this Letter we report the synthesis and evaluation of a series of non-amidine inhibitors of Urokinase Plasminogen Activator (uPA). Starting from compound 1, a significant change provided compounds in which the amidine, binding in the S1 pocket, was replaced with a primary amine. Further modifications led to the identification of potent, selective, and orally bioavailable uPA inhibitors.
-<!--
+Identification of orally bioavailable, non-amidine inhibitors of Urokinase Plasminogen Activator (uPA).,West CW, Adler M, Arnaiz D, Chen D, Chu K, Gualtieri G, Ho E, Huwe C, Light D, Phillips G, Pulk R, Sukovich D, Whitlow M, Yuan S, Bryant J Bioorg Med Chem Lett. 2009 Oct 1;19(19):5712-5. Epub 2009 Aug 7. PMID:19703768<ref>PMID:19703768</ref>
-The line below this paragraph, containing "STRUCTURE_3ig6", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_3ig6|  PDB=3ig6  |  SCENE=  }}
-===Low molecular weigth human Urokinase type Plasminogen activator 2-[6-(3'-Aminomethyl-biphenyl-3-yloxy)-4-(3-dimethylamino-pyrrolidin-1-yl)-3,5-difluoro-pyridin-2-yloxy]-4-dimethylamino-benzoic acid complex===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3ig6" style="background-color:#fffaf0;"></div>
+==See Also==
-<!--
+*[[Urokinase|Urokinase]]
-The line below this paragraph, {{ABSTRACT_PUBMED_19703768}}, adds the Publication Abstract to the page
+== References ==
-(as it appears on PubMed at http://www.pubmed.gov), where 19703768 is the PubMed ID number.
+<references/>
--->
+__TOC__
-{{ABSTRACT_PUBMED_19703768}}
+</StructureSection>
+[[Category: Human]]
-==Disease==
-Known disease associated with this structure: Alzheimer disease, late-onset, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191840 191840]]
-==About this Structure==
-IG6 is a 4 chains structure with sequences 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=3IG6 OCA].
-==Reference==
-<ref group="xtra">PMID:19703768</ref><references group="xtra"/>
-[[Category: Homo sapiens]]
 [[Category: U-plasminogen activator]]
-[[Category: Adler, M.]]
+[[Category: Adler, M]]
-[[Category: Whitlow, M.]]
+[[Category: Whitlow, M]]
 [[Category: Blood coagulation]]
 [[Category: Disulfide bond]]
@@ Line 38: / Line 50: @@
 [[Category: Hydrolase]]
 [[Category: Kringle]]
-[[Category: Pharmaceutical]]
 [[Category: Phosphoprotein]]
 [[Category: Plasminogen activation]]
-[[Category: Polymorphism]]
 [[Category: Protease]]
 [[Category: S1 site inhibitor]]
@@ Line 50: / Line 60: @@
 [[Category: Urokinase]]
 [[Category: Zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 28 15:04:05 2010''