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| | <StructureSection load='1u6q' size='340' side='right'caption='[[1u6q]], [[Resolution|resolution]] 2.02Å' scene=''> | | <StructureSection load='1u6q' size='340' side='right'caption='[[1u6q]], [[Resolution|resolution]] 2.02Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1u6q]] is a 1 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=1U6Q OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1U6Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1u6q]] 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=1U6Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U6Q FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=745:TRANS-6-(2-PHENYLCYCLOPROPYL)-NAPHTHALENE-2-CARBOXAMIDINE'>745</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.02Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1owd|1owd]], [[1owe|1owe]], [[1owh|1owh]], [[1owi|1owi]], [[1owj|1owj]], [[1sqa|1sqa]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=745:TRANS-6-(2-PHENYLCYCLOPROPYL)-NAPHTHALENE-2-CARBOXAMIDINE'>745</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1u6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u6q OCA], [https://pdbe.org/1u6q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u6q RCSB], [https://www.ebi.ac.uk/pdbsum/1u6q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u6q ProSAT]</span></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://proteopedia.org/fgij/fg.htm?mol=1u6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u6q OCA], [http://pdbe.org/1u6q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u6q RCSB], [http://www.ebi.ac.uk/pdbsum/1u6q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1u6q ProSAT]</span></td></tr> | + | |
| | </table> | | </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]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: U-plasminogen activator]]
| + | [[Category: Bruncko M]] |
| - | [[Category: Bruncko, M]] | + | [[Category: Dalton CR]] |
| - | [[Category: Dalton, C R]] | + | [[Category: Geyer A]] |
| - | [[Category: Geyer, A]] | + | [[Category: Giranda VL]] |
| - | [[Category: Giranda, V L]] | + | [[Category: Kaminski MK]] |
| - | [[Category: Kaminski, M K]] | + | [[Category: McClellan W]] |
| - | [[Category: McClellan, W]] | + | [[Category: Nienaber VL]] |
| - | [[Category: Nienaber, V L]] | + | [[Category: Rockway TR]] |
| - | [[Category: Rockway, T R]] | + | [[Category: Sauer DR]] |
| - | [[Category: Sauer, D R]] | + | [[Category: Wendt MD]] |
| - | [[Category: Wendt, M D]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| 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 PubMed
A series of non-amide-linked 6-substituted-2-naphthamidine urokinase plasminogen activator (uPA) inhibitors are described. These compounds possess excellent binding activities and selectivities with significantly improved pharmacokinetic profiles versus previously described amide-linked inhibitors.
Naphthamidine urokinase plasminogen activator inhibitors with improved pharmacokinetic properties.,Bruncko M, McClellan WJ, Wendt MD, Sauer DR, Geyer A, Dalton CR, Kaminski MA, Weitzberg M, Gong J, Dellaria JF, Mantei R, Zhao X, Nienaber VL, Stewart K, Klinghofer V, Bouska J, Rockway TW, Giranda VL Bioorg Med Chem Lett. 2005 Jan 3;15(1):93-8. PMID:15582418[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Paterson AD, Rommens JM, Bharaj B, Blavignac J, Wong I, Diamandis M, Waye JS, Rivard GE, Hayward CP. Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. Blood. 2010 Feb 11;115(6):1264-6. doi: 10.1182/blood-2009-07-233965. Epub 2009, Dec 9. PMID:20007542 doi:10.1182/blood-2009-07-233965
- ↑ Bruncko M, McClellan WJ, Wendt MD, Sauer DR, Geyer A, Dalton CR, Kaminski MA, Weitzberg M, Gong J, Dellaria JF, Mantei R, Zhao X, Nienaber VL, Stewart K, Klinghofer V, Bouska J, Rockway TW, Giranda VL. Naphthamidine urokinase plasminogen activator inhibitors with improved pharmacokinetic properties. Bioorg Med Chem Lett. 2005 Jan 3;15(1):93-8. PMID:15582418 doi:10.1016/j.bmcl.2004.10.026
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