|
|
| Line 1: |
Line 1: |
|
| |
|
| ==Urokinase type plasminogen activator== | | ==Urokinase type plasminogen activator== |
| <StructureSection load='1w0z' size='340' side='right'caption='[[1w0z]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='1w0z' size='340' side='right'caption='[[1w0z]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1w0z]] 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=1W0Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1W0Z FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0Z FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SI1:N-(BUTYLSULFONYL)-D-SERYL-N-{4-[AMINO(IMINO)METHYL]BENZYL}-L-ALANINAMIDE'>SI1</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | | </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=1w0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0z OCA], [https://pdbe.org/1w0z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w0z RCSB], [https://www.ebi.ac.uk/pdbsum/1w0z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0z ProSAT]</span></td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c5w|1c5w]], [[1c5x|1c5x]], [[1c5y|1c5y]], [[1c5z|1c5z]], [[1ejn|1ejn]], [[1f5k|1f5k]], [[1f5l|1f5l]], [[1f92|1f92]], [[1fv9|1fv9]], [[1gi7|1gi7]], [[1gi8|1gi8]], [[1gi9|1gi9]], [[1gj7|1gj7]], [[1gj8|1gj8]], [[1gj9|1gj9]], [[1gja|1gja]], [[1gjb|1gjb]], [[1gjc|1gjc]], [[1gjd|1gjd]], [[1kdu|1kdu]], [[1lmw|1lmw]], [[1o3p|1o3p]], [[1owd|1owd]], [[1owe|1owe]], [[1owh|1owh]], [[1owi|1owi]], [[1owj|1owj]], [[1owk|1owk]], [[1sqa|1sqa]], [[1sqo|1sqo]], [[1sqt|1sqt]], [[1urk|1urk]], [[1w10|1w10]], [[1w11|1w11]], [[1w12|1w12]], [[1w13|1w13]], [[1w14|1w14]]</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=1w0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0z OCA], [http://pdbe.org/1w0z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w0z RCSB], [http://www.ebi.ac.uk/pdbsum/1w0z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0z ProSAT]</span></td></tr> | |
| </table> | | </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 == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 23: |
Line 16: |
| </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=1w0z ConSurf]. | | </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=1w0z ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
| |
| == Publication Abstract from PubMed ==
| |
| Urokinase type plasminogen activator (uPA), a trypsin-like serine proteinase, plays an important role in normal tissue re-modelling, cell adhesion, and cell motility. In addition, studies utilizing normal animals and potent, selective uPA inhibitors or genetically modified mice that lack functional uPA genes have demonstrated that uPA can significantly enhance tumor initiation, growth, progression and metastasis, strongly suggesting that this enzyme may be a promising anti-cancer target. We have investigated the structure-activity relationship (SAR) of peptidomimetic inhibitors of uPA and solved high resolution X-ray structures of key, lead small molecule inhibitors (e.g. phenethylsulfonamidino(P4)-D-seryl(P3)-L-alanyl(P2)-L-argininal(P1) and derivatives thereof) in complex with the uPA proteinase domain. These potent inhibitors are highly selective for uPA. The non-natural D-seryl residue present at the P3 position in these inhibitors contributes substantially to both potency and selectivity because, due to its D-configuration, its side-chain binds in the S4 pocket to interact with the uPA unique residues Leu97b and His99. Additional potency and selectivity can be achieved by optimizing the inhibitor P4 residue to bind a pocket, known as S1sub or S1beta, that is adjacent to the primary specificity pocket of uPA.
| |
|
| |
| Crystals of urokinase type plasminogen activator complexes reveal the binding mode of peptidomimetic inhibitors.,Zeslawska E, Jacob U, Schweinitz A, Coombs G, Bode W, Madison E J Mol Biol. 2003 Apr 18;328(1):109-18. PMID:12684001<ref>PMID:12684001</ref>
| |
|
| |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| |
| </div>
| |
| <div class="pdbe-citations 1w0z" style="background-color:#fffaf0;"></div>
| |
|
| |
|
| ==See Also== | | ==See Also== |
| *[[Urokinase|Urokinase]] | | *[[Urokinase 3D Structures|Urokinase 3D Structures]] |
| == References ==
| |
| <references/>
| |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]]
| |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: U-plasminogen activator]]
| | [[Category: Jacob U]] |
| [[Category: Jacob, U]] | |
| [[Category: Hydrolase]]
| |
| [[Category: Plasminogen activator]]
| |
| [[Category: Urokinase]]
| |
