1db2

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[[Image:1db2.jpg|left|200px]]
 
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==CRYSTAL STRUCTURE OF NATIVE PLASMINOGEN ACTIVATOR INHIBITOR-1==
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The line below this paragraph, containing "STRUCTURE_1db2", creates the "Structure Box" on the page.
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<StructureSection load='1db2' size='340' side='right'caption='[[1db2]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1db2]] is a 2 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=1DB2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DB2 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.7&#8491;</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=1db2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1db2 OCA], [https://pdbe.org/1db2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1db2 RCSB], [https://www.ebi.ac.uk/pdbsum/1db2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1db2 ProSAT]</span></td></tr>
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{{STRUCTURE_1db2| PDB=1db2 | SCENE= }}
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</table>
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== Disease ==
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[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.
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== Function ==
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[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>
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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/db/1db2_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=1db2 ConSurf].
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<div style="clear:both"></div>
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'''CRYSTAL STRUCTURE OF NATIVE PLASMINOGEN ACTIVATOR INHIBITOR-1'''
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==See Also==
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*[[Plasminogen activator inhibitor|Plasminogen activator inhibitor]]
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== References ==
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==Overview==
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<references/>
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The crystal structure of a constitutively active multiple site mutant of plasminogen activator inhibitor 1 (PAI-1) was determined and refined at a resolution of 2.7 A.The present structure comprises a dimer of two crystallographically independent PAI-1 molecules that pack by association of the residues P6 to P3 of the reactive centre loop of one molecule (A) with the edge of the main beta-sheet A of the other molecule (B).Thus, the reactive centre loop is ordered for molecule A by crystal packing forces, while for molecule B it is unconstrained by crystal packing contacts and is disordered.The overall structure of active PAI-1 is similar to the structures of other active inhibitory serpins exhibiting as the major secondary structural feature a five-stranded beta-sheet A and an intact proteinase-binding loop protruding from the one end of the elongated molecule. No preinsertion of the reactive centre loop is observed in this structure.A comparison of the present structure with the previously determined crystal structures of PAI-1 in its alternative conformations reveals that, upon cleavage of an intact form of PAI-1 or formation of latent PAI-1, the well-characterised rearrangements of the serpin secondary structural elements are accompanied by dramatic and partly unexpected conformational changes of helical and loop structures proximal to beta-sheet A.The present structure explains the stabilising effects of the mutated residues, reveals the structural cause for the observed spectroscopic differences between active and latent PAI-1, and provides new insights into possible mechanisms of stabilisation by its natural binding partner, vitronectin.
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__TOC__
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</StructureSection>
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==About this Structure==
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1DB2 is a [[Single protein]] structure of 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=1DB2 OCA].
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==Reference==
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Plasminogen activator inhibitor 1. Structure of the native serpin, comparison to its other conformers and implications for serpin inactivation., Nar H, Bauer M, Stassen JM, Lang D, Gils A, Declerck PJ, J Mol Biol. 2000 Mar 31;297(3):683-95. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10731421 10731421]
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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: Bauer, M.]]
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[[Category: Bauer M]]
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[[Category: Declerck, P.]]
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[[Category: Declerck P]]
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[[Category: Gils, A.]]
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[[Category: Gils A]]
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[[Category: Lang, D.]]
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[[Category: Lang D]]
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[[Category: Nar, H.]]
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[[Category: Nar H]]
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[[Category: Stassen, J M.]]
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[[Category: Stassen JM]]
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[[Category: Hydrolase inhibitor]]
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[[Category: Native serpin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:39:01 2008''
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CRYSTAL STRUCTURE OF NATIVE PLASMINOGEN ACTIVATOR INHIBITOR-1

PDB ID 1db2

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