1oc0: Difference between revisions

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New page: left|200px<br /> <applet load="1oc0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1oc0, resolution 2.28Å" /> '''PLASMINOGEN ACTIVAT...
 
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[[Image:1oc0.gif|left|200px]]<br />
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'''PLASMINOGEN ACTIVATOR INHIBITOR-1 COMPLEX WITH SOMATOMEDIN B DOMAIN OF VITRONECTIN'''<br />


==Overview==
==plasminogen activator inhibitor-1 complex with somatomedin B domain of vitronectin==
The interaction of the plasma protein vitronectin with plasminogen, activator inhibitor-1 (PAI-1) is central to human health. Vitronectin, binding extends the lifetime of active PAI-1, which controls hemostasis by, inhibiting fibrinolysis and has also been implicated in angiogenesis. The, PAI-1-vitronectin binding interaction also affects cell adhesion and, motility. For these reasons, elevated PAI-1 activities are associated both, with coronary thrombosis and with a poor prognosis in many cancers. Here, we show the crystal structure at a resolution of 2.3 A of the complex of, the somatomedin B domain of vitronectin with PAI-1. The structure of the, complex explains how vitronectin binds to and stabilizes the active, conformation of PAI-1. It also explains the tissue effects of PAI-1, as, PAI-1 competes for and sterically blocks the interaction of vitronectin, with cell surface receptors and integrins. Structural understanding of the, essential biological roles of the interaction between PAI-1 and, vitronectin opens the prospect of specifically designed blocking agents, for the prevention of thrombosis and treatment of cancer.
<StructureSection load='1oc0' size='340' side='right'caption='[[1oc0]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1oc0]] 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=1OC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OC0 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]] 2.28&#8491;</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=1oc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oc0 OCA], [https://pdbe.org/1oc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oc0 RCSB], [https://www.ebi.ac.uk/pdbsum/1oc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oc0 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/oc/1oc0_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=1oc0 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The interaction of the plasma protein vitronectin with plasminogen activator inhibitor-1 (PAI-1) is central to human health. Vitronectin binding extends the lifetime of active PAI-1, which controls hemostasis by inhibiting fibrinolysis and has also been implicated in angiogenesis. The PAI-1-vitronectin binding interaction also affects cell adhesion and motility. For these reasons, elevated PAI-1 activities are associated both with coronary thrombosis and with a poor prognosis in many cancers. Here we show the crystal structure at a resolution of 2.3 A of the complex of the somatomedin B domain of vitronectin with PAI-1. The structure of the complex explains how vitronectin binds to and stabilizes the active conformation of PAI-1. It also explains the tissue effects of PAI-1, as PAI-1 competes for and sterically blocks the interaction of vitronectin with cell surface receptors and integrins. Structural understanding of the essential biological roles of the interaction between PAI-1 and vitronectin opens the prospect of specifically designed blocking agents for the prevention of thrombosis and treatment of cancer.


==Disease==
How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration.,Zhou A, Huntington JA, Pannu NS, Carrell RW, Read RJ Nat Struct Biol. 2003 Jul;10(7):541-4. PMID:12808446<ref>PMID:12808446</ref>
Known diseases associated with this structure: Hemorrhagic diathesis due to PAI1 deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173360 173360]], Thrombophilia due to excessive plasminogen activator inhibitor OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173360 173360]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1OC0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1OC0 OCA].
</div>
<div class="pdbe-citations 1oc0" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration., Zhou A, Huntington JA, Pannu NS, Carrell RW, Read RJ, Nat Struct Biol. 2003 Jul;10(7):541-4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12808446 12808446]
*[[Plasminogen activator inhibitor|Plasminogen activator inhibitor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Carrell, R.W.]]
[[Category: Carrell RW]]
[[Category: Huntington, J.A.]]
[[Category: Huntington JA]]
[[Category: Pannu, N.S.]]
[[Category: Pannu NS]]
[[Category: Read, R.J.]]
[[Category: Read RJ]]
[[Category: Zhou, A.]]
[[Category: Zhou A]]
[[Category: cell adhesion]]
[[Category: cell migration]]
[[Category: fibrinolysis]]
[[Category: heparin-binding]]
[[Category: plasminogen activation]]
[[Category: proteinase inhibitor]]
[[Category: serpin]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:31:23 2007''

Latest revision as of 10:32, 23 October 2024

plasminogen activator inhibitor-1 complex with somatomedin B domain of vitronectinplasminogen activator inhibitor-1 complex with somatomedin B domain of vitronectin

Structural highlights

1oc0 is a 2 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 2.28Å
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.

Publication Abstract from PubMed

The interaction of the plasma protein vitronectin with plasminogen activator inhibitor-1 (PAI-1) is central to human health. Vitronectin binding extends the lifetime of active PAI-1, which controls hemostasis by inhibiting fibrinolysis and has also been implicated in angiogenesis. The PAI-1-vitronectin binding interaction also affects cell adhesion and motility. For these reasons, elevated PAI-1 activities are associated both with coronary thrombosis and with a poor prognosis in many cancers. Here we show the crystal structure at a resolution of 2.3 A of the complex of the somatomedin B domain of vitronectin with PAI-1. The structure of the complex explains how vitronectin binds to and stabilizes the active conformation of PAI-1. It also explains the tissue effects of PAI-1, as PAI-1 competes for and sterically blocks the interaction of vitronectin with cell surface receptors and integrins. Structural understanding of the essential biological roles of the interaction between PAI-1 and vitronectin opens the prospect of specifically designed blocking agents for the prevention of thrombosis and treatment of cancer.

How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration.,Zhou A, Huntington JA, Pannu NS, Carrell RW, Read RJ Nat Struct Biol. 2003 Jul;10(7):541-4. PMID:12808446[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
  3. Zhou A, Huntington JA, Pannu NS, Carrell RW, Read RJ. How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration. Nat Struct Biol. 2003 Jul;10(7):541-4. PMID:12808446 doi:10.1038/nsb943

1oc0, resolution 2.28Å

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