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| | ==Crystal structure of the free aminoterminal fragment of urokinase type plasminogen activator (ATF)== | | ==Crystal structure of the free aminoterminal fragment of urokinase type plasminogen activator (ATF)== |
| - | <StructureSection load='2i9a' size='340' side='right' caption='[[2i9a]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='2i9a' size='340' side='right'caption='[[2i9a]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2i9a]] 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=2I9A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2I9A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2i9a]] is a 4 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=2I9A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I9A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2i9b|2i9b]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=2i9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i9a OCA], [https://pdbe.org/2i9a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i9a RCSB], [https://www.ebi.ac.uk/pdbsum/2i9a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i9a 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2i9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i9a OCA], [http://pdbe.org/2i9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i9a RCSB], [http://www.ebi.ac.uk/pdbsum/2i9a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2i9a 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]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i9/2i9a_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i9/2i9a_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2i9a" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2i9a" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Urokinase 3D Structures|Urokinase 3D Structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: U-plasminogen activator]] | + | [[Category: Large Structures]] |
| - | [[Category: Barinka, C]] | + | [[Category: Barinka C]] |
| - | [[Category: Lubkowski, J]] | + | [[Category: Lubkowski J]] |
| - | [[Category: Growth factor-like domain]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Kringle domain]]
| + | |
| 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
Recent studies indicate that binding of the urokinase-type plasminogen activator (uPA) to its high-affinity receptor (uPAR) orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes, including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known about the exact mode of uPAR/uPA interactions or the presumed conformational changes that accompany uPA/uPAR engagement. Here, we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell-surface anchoring sequence, in complex with the amino-terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 A. We report the 1.9 A crystal structure of free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR/uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding.
Structural basis of interaction between urokinase-type plasminogen activator and its receptor.,Barinka C, Parry G, Callahan J, Shaw DE, Kuo A, Bdeir K, Cines DB, Mazar A, Lubkowski J J Mol Biol. 2006 Oct 20;363(2):482-95. Epub 2006 Aug 26. PMID:16979660[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
- ↑ Barinka C, Parry G, Callahan J, Shaw DE, Kuo A, Bdeir K, Cines DB, Mazar A, Lubkowski J. Structural basis of interaction between urokinase-type plasminogen activator and its receptor. J Mol Biol. 2006 Oct 20;363(2):482-95. Epub 2006 Aug 26. PMID:16979660 doi:10.1016/j.jmb.2006.08.063
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