3ig6

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{{STRUCTURE_3ig6| PDB=3ig6 | SCENE= }}
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==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==
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===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===
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<StructureSection load='3ig6' size='340' side='right' caption='[[3ig6]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
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{{ABSTRACT_PUBMED_19703768}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3ig6]] is a 4 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=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>
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</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>
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<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>
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<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 Homo sapiens])</td></tr>
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<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>
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<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://www.rcsb.org/pdb/explore.do?structureId=3ig6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ig6 PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[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>
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== Function ==
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[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ig/3ig6_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==Disease==
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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>
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[[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>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
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</div>
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==About this Structure==
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[[3ig6]] is a 4 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=3IG6 OCA].
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==See Also==
==See Also==
*[[Urokinase|Urokinase]]
*[[Urokinase|Urokinase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019703768</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: U-plasminogen activator]]
[[Category: U-plasminogen activator]]
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[[Category: Adler, M.]]
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[[Category: Adler, M]]
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[[Category: Whitlow, M.]]
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[[Category: Whitlow, M]]
[[Category: Blood coagulation]]
[[Category: Blood coagulation]]
[[Category: Disulfide bond]]
[[Category: Disulfide bond]]

Revision as of 15:07, 18 December 2014

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

3ig6, resolution 1.83Å

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