1b3k: Difference between revisions

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<StructureSection load='1b3k' size='340' side='right'caption='[[1b3k]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
<StructureSection load='1b3k' size='340' side='right'caption='[[1b3k]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1b3k]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B3K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1B3K FirstGlance]. <br>
<table><tr><td colspan='2'>[[1b3k]] 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=1B3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B3K FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c5g|1c5g]]</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.99&#8491;</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=1b3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b3k OCA], [http://pdbe.org/1b3k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1b3k RCSB], [http://www.ebi.ac.uk/pdbsum/1b3k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1b3k ProSAT]</span></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=1b3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b3k OCA], [https://pdbe.org/1b3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1b3k RCSB], [https://www.ebi.ac.uk/pdbsum/1b3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1b3k ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== 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.  
[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 ==
== 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>
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=1b3k ConSurf].
</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=1b3k ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: Plasminogen activator inhibitor 1 (PAI-1) is a serpin that has a key role in the control of fibrinolysis through proteinase inhibition. PAI-1 also has a role in regulating cell adhesion processes relevant to tissue remodeling and metastasis; this role is mediated by its binding to the adhesive glycoprotein vitronectin rather than by proteinase inhibition. Active PAI-1 is metastable and spontaneously transforms to an inactive latent conformation. Previous attempts to crystallize the active conformation of PAI-1 have failed. RESULTS: The crystal structure of a stable quadruple mutant of PAI-1(Asn150--&gt;His, Lys154--&gt;Thr, Gln319--&gt;Leu, Met354--&gt;Ile) in its active conformation has been solved at a nominal 3 A resolution. In two of four independent molecules within the crystal, the flexible reactive center loop is unconstrained by crystal-packing contacts and is disordered. In the other two molecules, the reactive center loop forms intimate loop-sheet interactions with neighboring molecules, generating an infinite chain within the crystal. The overall conformation resembles that seen for other active inhibitory serpins. CONCLUSIONS: The structure clarifies the molecular basis of the stabilizing mutations and the reduced affinity of PAI-1, on cleavage or in the latent form, for vitronectin. The infinite chain of linked molecules also suggests a new mechanism for the serpin polymerization associated with certain diseases. The results support the concept that the reactive center loop of an active serpin is flexible and has no defined conformation in the absence of intermolecular contacts. The determination of the structure of the active form constitutes an essential step for the rational design of PAI-1 inhibitors.
The active conformation of plasminogen activator inhibitor 1, a target for drugs to control fibrinolysis and cell adhesion.,Sharp AM, Stein PE, Pannu NS, Carrell RW, Berkenpas MB, Ginsburg D, Lawrence DA, Read RJ Structure. 1999 Feb 15;7(2):111-8. PMID:10368279<ref>PMID:10368279</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1b3k" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Pannu, N S]]
[[Category: Pannu NS]]
[[Category: Read, R J]]
[[Category: Read RJ]]
[[Category: Sharp, A M]]
[[Category: Sharp AM]]
[[Category: Stein, P E]]
[[Category: Stein PE]]
[[Category: Blood clotting]]
[[Category: Inhibitor]]
[[Category: Pai-1]]
[[Category: Serpin]]

Latest revision as of 08:55, 3 April 2024

Plasminogen activator inhibitor-1Plasminogen activator inhibitor-1

Structural highlights

1b3k is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.99Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PAI1_HUMAN Defects in SERPINE1 are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1D) [MIM: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.[1] Note=High concentrations of SERPINE1 seem to contribute to the development of venous but not arterial occlusions.

Function

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.[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Fay WP, Parker AC, Condrey LR, Shapiro AD. Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene. Blood. 1997 Jul 1;90(1):204-8. PMID:9207454
  2. ↑ Szabo R, Netzel-Arnett S, Hobson JP, Antalis TM, Bugge TH. Matriptase-3 is a novel phylogenetically preserved membrane-anchored serine protease with broad serpin reactivity. Biochem J. 2005 Aug 15;390(Pt 1):231-42. PMID:15853774 doi:BJ20050299

1b3k, resolution 2.99Å

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