1a7c: Difference between revisions

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-[[Image:1a7c.png|left|200px]]
-{{STRUCTURE_1a7c|  PDB=1a7c  |  SCENE=  }}
+==HUMAN PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 IN COMPLEX WITH A PENTAPEPTIDE==
+<StructureSection load='1a7c' size='340' side='right'caption='[[1a7c]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1a7c]] is a 3 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=1A7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A7C 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]] 1.95&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=RIP:RIBOSE(PYRANOSE+FORM)'>RIP</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=1a7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a7c OCA], [https://pdbe.org/1a7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a7c RCSB], [https://www.ebi.ac.uk/pdbsum/1a7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a7c ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PAI1_HUMAN PAI1_HUMAN] Defects in SERPINE1 are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1D) [MIM:[https://omim.org/entry/613329 613329]. It is a hematologic disorder characterized by increased bleeding after trauma, injury, or surgery. Affected females have menorrhagia. The bleeding defect is due to increased fibrinolysis of fibrin blood clots due to deficiency of plasminogen activator inhibitor-1, which inhibits tissue and urinary activators of plasminogen.<ref>PMID:9207454</ref>   Note=High concentrations of SERPINE1 seem to contribute to the development of venous but not arterial occlusions.
+== Function ==
+[https://www.uniprot.org/uniprot/PAI1_HUMAN PAI1_HUMAN] Serine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. Its rapid interaction with PLAT may function as a major control point in the regulation of fibrinolysis.<ref>PMID:15853774</ref>
+== 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/a7/1a7c_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=1a7c ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is an important endogenous regulator of the fibrinolytic system. Reduction of PAI-1 activity has been shown to enhance dissolution of blood clots. Like other serpins, PAI-1 binds covalently to a target serine protease, thereby irreversibly inactivating the enzyme. During this process the exposed reactive-centre loop of PAI-1 is believed to undergo a conformational change becoming inserted into beta sheet A of the serpin. Incubation with peptides from the reactive-centre loop transform serpins into a substrate for their target protease. It has been hypothesised that these peptides bind to beta sheet A, thereby hindering the conformational rearrangement leading to loop insertion and formation of the stable serpin-protease complex. RESULTS: We report here the 1.95 A X-ray crystal structure of a complex of a glycosylated mutant of PAI-1, PAI-1-ala335Glu, with two molecules of the inhibitory reactive-centre loop peptide N-Ac-TVASS-NH2. Both bound peptide molecules are located between beta strands 3A and 5A of the serpin. The binding kinetics of the peptide inhibitor to immobilised PAI-1-Ala335Glu, as monitored by surface plasmon resonance, is consistent with there being two different binding sites. CONCLUSIONS: This is the first reported crystal structure of a complex formed between a serpin and a serpin inhibitor. The localisation of the inhibitory peptide in the complex strongly supports the theory that molecules binding in the space between beta strands 3A and 5A of a serpin are able to prevent insertion of the reactive-centre loop into beta sheet A, thereby abolishing the ability of the serpin to irreversibly inactivate its target enzyme. The characterisation of the two binding sites for the peptide inhibitor provides a solid foundation for computer-aided design of novel, low molecular weight PAI-1 inhibitors.
-===HUMAN PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 IN COMPLEX WITH A PENTAPEPTIDE===
+Interfering with the inhibitory mechanism of serpins: crystal structure of a complex formed between cleaved plasminogen activator inhibitor type 1 and a reactive-centre loop peptide.,Xue Y, Bjorquist P, Inghardt T, Linschoten M, Musil D, Sjolin L, Deinum J Structure. 1998 May 15;6(5):627-36. PMID:9634700<ref>PMID:9634700</ref>
-{{ABSTRACT_PUBMED_9634700}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 1a7c" style="background-color:#fffaf0;"></div>
-[[1a7c]] is a 3 chain structure of [[Plasminogen activator inhibitor]] 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=1A7C OCA].
 ==See Also==
 *[[Plasminogen activator inhibitor|Plasminogen activator inhibitor]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:009634700</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Deinum, J.]]
+[[Category: Large Structures]]
-[[Category: Inghardt, T.]]
+[[Category: Deinum J]]
-[[Category: Sjolin, L.]]
+[[Category: Inghardt T]]
-[[Category: Xue, Y.]]
+[[Category: Sjolin L]]
-[[Category: Carbohydrate]]
+[[Category: Xue Y]]
-[[Category: Hydrolase inhibitor-peptide complex]]
-[[Category: Inhibitor complex]]
-[[Category: Pai-1]]
-[[Category: Protease inhibitor-peptide complex]]
-[[Category: Serine protease inhibitor]]