3ig6: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| (9 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
''' | ==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== | ||
<StructureSection load='3ig6' size='340' side='right' caption='[[3ig6]], [[Resolution|resolution]] 1.83Å' 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> | |||
From MEDLINE®/PubMed®, 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]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human]] | |||
[[Category: U-plasminogen activator]] | |||
[[Category: Adler, M]] | |||
[[Category: Whitlow, M]] | |||
[[Category: Blood coagulation]] | |||
[[Category: Disulfide bond]] | |||
[[Category: Egf-like domain]] | |||
[[Category: Fibrinolysis]] | |||
[[Category: Glycoprotein]] | |||
[[Category: Hydrolase]] | |||
[[Category: Kringle]] | |||
[[Category: Phosphoprotein]] | |||
[[Category: Plasminogen activation]] | |||
[[Category: Protease]] | |||
[[Category: S1 site inhibitor]] | |||
[[Category: Secreted]] | |||
[[Category: Selective]] | |||
[[Category: Serine protease]] | |||
[[Category: Structure-based drug design]] | |||
[[Category: Urokinase]] | |||
[[Category: Zymogen]] | |||
Latest revision as of 09:04, 9 February 2016
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 complexLow 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
Structural highlights
Disease[UROK_HUMAN] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM: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.[1] Function[UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIn 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||
