1f92: Difference between revisions

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<StructureSection load='1f92' size='340' side='right'caption='[[1f92]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='1f92' size='340' side='right'caption='[[1f92]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1f92]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F92 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1f92]] 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=1F92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F92 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UKP:[2,4,6-TRIISOPROPYL-PHENYLSULFONYL-L-[3-AMIDINO-PHENYLALANINYL]]-N-BETA-ALANINYL-PIPERAZINE'>UKP</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]] 2.6&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ejn|1ejn]], [[1f5k|1f5k]], [[1f5l|1f5l]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UKP:[2,4,6-TRIISOPROPYL-PHENYLSULFONYL-L-[3-AMIDINO-PHENYLALANINYL]]-N-BETA-ALANINYL-PIPERAZINE'>UKP</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=1f92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f92 OCA], [https://pdbe.org/1f92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f92 RCSB], [https://www.ebi.ac.uk/pdbsum/1f92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f92 ProSAT]</span></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=1f92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f92 OCA], [https://pdbe.org/1f92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f92 RCSB], [https://www.ebi.ac.uk/pdbsum/1f92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f92 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[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>
[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 ==
[[https://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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</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=1f92 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=1f92 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Urokinase is a serine protease involved in cancer growth and metastasis. Here we present the first urokinase crystal structure in complex with reversible inhibitors at 2.1 and 2.6 A resolution. These inhibitor complex structures have been obtained from crystals of engineered urokinase type plasminogen activator designed to obtain a crystal form open for inhibitor soaking. The mutant C122S loses its flexible A-chain upon activation cleavage and crystallizes in the presence of benzamidine, which was later displaced by the desired inhibitor. This new soakable crystal form turned out to be of great value in the process of structure-based drug design. The evaluated binding mode of amiloride, and UKI-1D revealed a new subsite of the primary specificity pocket of urokinase that will be employed in the future ligand optimisation process.
Crystals of the urokinase type plasminogen activator variant beta(c)-uPAin complex with small molecule inhibitors open the way towards structure-based drug design.,Zeslawska E, Schweinitz A, Karcher A, Sondermann P, Sperl S, Sturzebecher J, Jacob U J Mol Biol. 2000 Aug 11;301(2):465-75. PMID:10926521<ref>PMID:10926521</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1f92" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: U-plasminogen activator]]
[[Category: Jacob U]]
[[Category: Jacob, U]]
[[Category: Karcher A]]
[[Category: Karcher, A]]
[[Category: Schweinitz A]]
[[Category: Schweinitz, A]]
[[Category: Sondermann P]]
[[Category: Sondermann, P]]
[[Category: Sperl S]]
[[Category: Sperl, S]]
[[Category: Sturzebecher J]]
[[Category: Sturzebecher, J]]
[[Category: Zeslawska E]]
[[Category: Zeslawska, E]]
[[Category: Hydrolase]]
[[Category: Inhibitor]]
[[Category: Serine protease]]
[[Category: Urokinase]]

Latest revision as of 10:11, 20 March 2024

UROKINASE PLASMINOGEN ACTIVATOR B CHAIN-UKI-1D COMPLEX

1f92, resolution 2.60Å

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