9pai
From Proteopedia
(Difference between revisions)
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| - | + | ==CLEAVED SUBSTRATE VARIANT OF PLASMINOGEN ACTIVATOR INHIBITOR-1== | |
| - | + | <StructureSection load='9pai' size='340' side='right' caption='[[9pai]], [[Resolution|resolution]] 2.70Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[9pai]] is a 2 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=9PAI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=9PAI FirstGlance]. <br> | ||
| + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=9pai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pai OCA], [http://www.rcsb.org/pdb/explore.do?structureId=9pai RCSB], [http://www.ebi.ac.uk/pdbsum/9pai PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/PAI1_HUMAN PAI1_HUMAN]] Defects in SERPINE1 are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1D) [MIM:[http://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 == | ||
| + | [[http://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/pa/9pai_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Plasminogen activator inhibitor-1 (PAI-1) is unique among the serine proteinase inhibitors (serpins) in that it can adopt at least three different conformations (active, substrate and latent). We report the X-ray structure of a cleaved substrate variant of human PAI-1, which has a new beta-strand s4A formed by insertion of the amino-terminal portion of the reactive-site loop into beta-sheet A subsequent to cleavage. This is in contrast to the previous suggestion that the non-inhibitory function of substrate-type serpins is mainly due to an inability of the reactive-site loop to adopt this conformation. Comparison with the structure of latent PAI-1 provides insights into the molecular determinants responsible for the transition of the stressed active conformation to the thermostable latent conformation. | ||
| - | + | Mechanisms contributing to the conformational and functional flexibility of plasminogen activator inhibitor-1.,Aertgeerts K, De Bondt HL, De Ranter CJ, Declerck PJ Nat Struct Biol. 1995 Oct;2(10):891-7. PMID:7552714<ref>PMID:7552714</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Plasminogen activator inhibitor|Plasminogen activator inhibitor]] | *[[Plasminogen activator inhibitor|Plasminogen activator inhibitor]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Aertgeerts, K | + | [[Category: Aertgeerts, K]] |
| - | [[Category: Bondt, H L.De | + | [[Category: Bondt, H L.De]] |
| - | [[Category: Declerck, P J | + | [[Category: Declerck, P J]] |
| - | [[Category: Ranter, C J.De | + | [[Category: Ranter, C J.De]] |
[[Category: Hydrolase inhibitor]] | [[Category: Hydrolase inhibitor]] | ||
[[Category: Serpin]] | [[Category: Serpin]] | ||
Revision as of 15:04, 21 December 2014
CLEAVED SUBSTRATE VARIANT OF PLASMINOGEN ACTIVATOR INHIBITOR-1
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