1lmw: Difference between revisions

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-{{STRUCTURE_1lmw|  PDB=1lmw  |  SCENE=  }}
-===LMW U-PA Structure complexed with EGRCMK (GLU-GLY-ARG Chloromethyl Ketone)===
-{{ABSTRACT_PUBMED_8591045}}
-==Disease==
+==LMW U-PA Structure complexed with EGRCMK (GLU-GLY-ARG Chloromethyl Ketone)==
-[[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>
+<StructureSection load='1lmw' size='340' side='right'caption='[[1lmw]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1lmw]] 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=1LMW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LMW FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0GJ:L-ALPHA-GLUTAMYL-N-{(1S)-4-{[AMINO(IMINIO)METHYL]AMINO}-1-[(1S)-2-CHLORO-1-HYDROXYETHYL]BUTYL}GLYCINAMIDE'>0GJ</scene></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=1lmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lmw OCA], [https://pdbe.org/1lmw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lmw RCSB], [https://www.ebi.ac.uk/pdbsum/1lmw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lmw ProSAT]</span></td></tr>
+</table>
+== 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>
+== Function ==
+[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lm/1lmw_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1lmw ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+BACKGROUND: Urokinase-type plasminogen activator (u-PA) promotes fibrinolysis by catalyzing the conversion of plasminogen to the active protease plasmin via the cleavage of a peptide bond. When localized to the external cell surface it contributes to tissue remodelling and cellular migration; inhibition of its activity impedes the spread of cancer. u-PA has three domains: an N-terminal receptor-binding growth factor domain, a central kringle domain and a C-terminal catalytic protease domain. The biological roles of the fibrinolytic enzymes render them therapeutic targets, however, until now no structure of the protease domain has been available. Solution of the structure of the u-PA serine protease was undertaken to provide such data. RESULTS: The crystal structure of the catalytic domain of recombinant, non-glycosylated human u-PA, complexed with the inhibitor Glu-Gly-Arg chloromethyl ketone (EGRcmk), has been determined at a nominal resolution of 2.5 A and refined to a crystallographic R-factor of 22.4% on all data (20.4% on data &gt; 3 sigma). The enzyme has the expected topology of a trypsin-like serine protease. CONCLUSIONS: The enzyme has an S1 specificity pocket similar to that of trypsin, a restricted, less accessible, hydrophobic S2 pocket and a solvent-accessible S3 pocket which is capable of accommodating a wide range of residues. The EGRcmk inhibitor binds covalently at the active site to form a tetrahedral hemiketal structure. Although the overall structure is similar to that of homologous serine proteases, at six positions insertions of extra residues in loop regions create unique surface areas. One of these loop regions is highly mobile despite being anchored by the disulphide bridge which is characteristic of a small subset of serine proteases namely tissuetype plasminogen activator, Factor XII and Complement Factor I.
-==Function==
+The crystal structure of the catalytic domain of human urokinase-type plasminogen activator.,Spraggon G, Phillips C, Nowak UK, Ponting CP, Saunders D, Dobson CM, Stuart DI, Jones EY Structure. 1995 Jul 15;3(7):681-91. PMID:8591045<ref>PMID:8591045</ref>
-[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[1lmw]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LMW OCA].
+</div>
+<div class="pdbe-citations 1lmw" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Urokinase|Urokinase]]
+*[[Urokinase 3D Structures|Urokinase 3D Structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:008591045</ref><references group="xtra"/><references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: U-plasminogen activator]]
+[[Category: Large Structures]]
-[[Category: Dobson, C M.]]
+[[Category: Dobson CM]]
-[[Category: Jones, E Y.]]
+[[Category: Jones EY]]
-[[Category: Nowak, U K.]]
+[[Category: Nowak UK]]
-[[Category: Phillips, C.]]
+[[Category: Phillips C]]
-[[Category: Ponting, C P.]]
+[[Category: Ponting CP]]
-[[Category: Saunders, D.]]
+[[Category: Saunders D]]
-[[Category: Spraggon, G S.]]
+[[Category: Spraggon GS]]
-[[Category: Stuart, D I.]]
+[[Category: Stuart DI]]
-[[Category: Fibrinolysis]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Serine protease]]
-[[Category: Trypsin-like serine protease]]