1f5l

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[[Image:1f5l.jpg|left|200px]]<br /><applet load="1f5l" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1f5l, resolution 2.1&Aring;" />
 
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'''UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-AMILORIDE COMPLEX'''<br />
 
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==Overview==
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==UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-AMILORIDE COMPLEX==
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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.
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<StructureSection load='1f5l' size='340' side='right'caption='[[1f5l]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1f5l]] 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=1F5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F5L FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMR:3,5-DIAMINO-N-(AMINOIMINOMETHYL)-6-CHLOROPYRAZINECARBOXAMIDE'>AMR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1f5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f5l OCA], [https://pdbe.org/1f5l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f5l RCSB], [https://www.ebi.ac.uk/pdbsum/1f5l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f5l ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f5/1f5l_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1f5l ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known disease associated with this structure: Alzheimer disease, late-onset, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191840 191840]]
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*[[Urokinase 3D Structures|Urokinase 3D Structures]]
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== References ==
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==About this Structure==
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<references/>
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1F5L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=AMR:'>AMR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F5L OCA].
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__TOC__
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</StructureSection>
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==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10926521 10926521]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: U-plasminogen activator]]
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[[Category: Jacob U]]
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[[Category: Jacob, U.]]
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[[Category: Karcher A]]
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[[Category: Karcher, A.]]
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[[Category: Schweinitz A]]
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[[Category: Schweinitz, A.]]
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[[Category: Sondermann P]]
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[[Category: Sondermann, P.]]
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[[Category: Sperl S]]
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[[Category: Sperl, S.]]
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[[Category: Sturzebecher J]]
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[[Category: Sturzebecher, J.]]
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[[Category: Zeslawska E]]
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[[Category: Zeslawska, E.]]
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[[Category: AMR]]
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[[Category: SO4]]
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[[Category: human]]
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[[Category: inhibitor]]
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[[Category: serine protease]]
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[[Category: urokinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:46:00 2008''
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Current revision

UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-AMILORIDE COMPLEX

PDB ID 1f5l

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