3cvm

From Proteopedia

(Difference between revisions)

Revision as of 13:10, 7 November 2018

High resolution structure of a stable Plasminogen activator inhibitor type-1 in its protease cleaved form

Structural highlights

3cvm 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.
Related:	9pai
Gene:	SERPINE1, PAI1, PLANH1 (Homo sapiens)
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

Wild-type plasminogen activator inhibitor type-1 (PAI-1) rapidly converts to the inactive latent state under conditions of physiological pH and temperature. For in vivo studies of active PAI-1 in cell culture and in vivo model systems, the 14-1B PAI-1 mutant (N150H-K154T-Q319L-M354I), with its stabilized active conformation, has thus become the PAI-1 of choice. As a consequence of the increased stability, the only two forms likely to be encountered are the active or the cleaved form, the latter either free or complexed with target proteinase. We hereby report the first structure of the stable 14-1B PAI-1 variant in its reactive center cleaved form, to a resolution of 2.0 A. The >99% complete structure represents the highest resolved structure of free cleaved PAI-1. This high-resolution structure should be of great use for drug target development and for modeling protein-protein interactions such as those of PAI-1 with vitronectin.

High-resolution structure of the stable plasminogen activator inhibitor type-1 variant 14-1B in its proteinase-cleaved form: a new tool for detailed interaction studies and modeling.,Jensen JK, Gettins PG Protein Sci. 2008 Oct;17(10):1844-9. Epub 2008 Aug 25. PMID:18725454^[3]

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

References

↑ 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
↑ 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
↑ Jensen JK, Gettins PG. High-resolution structure of the stable plasminogen activator inhibitor type-1 variant 14-1B in its proteinase-cleaved form: a new tool for detailed interaction studies and modeling. Protein Sci. 2008 Oct;17(10):1844-9. Epub 2008 Aug 25. PMID:18725454 doi:10.1110/ps.036707.108

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3cvm"

@@ Line 1: / Line 1: @@
 ==High resolution structure of a stable Plasminogen activator inhibitor type-1 in its protease cleaved form==
 <StructureSection load='3cvm' size='340' side='right' caption='[[3cvm]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[9pai|9pai]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SERPINE1, PAI1, PLANH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3cvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cvm OCA], [http://pdbe.org/3cvm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cvm RCSB], [http://www.ebi.ac.uk/pdbsum/3cvm PDBsum]</span></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=3cvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cvm OCA], [http://pdbe.org/3cvm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cvm RCSB], [http://www.ebi.ac.uk/pdbsum/3cvm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cvm ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cv/3cvm_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cv/3cvm_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 45: / Line 46: @@
 [[Category: Plasminogen activation]]
 [[Category: Plasminogen activator inhibitor type-1]]
+[[Category: Polymorphism]]
 [[Category: Protease inhibitor]]
 [[Category: Secreted]]
 [[Category: Serine protease inhibitor]]

3cvm

From Proteopedia

Revision as of 13:10, 7 November 2018

High resolution structure of a stable Plasminogen activator inhibitor type-1 in its protease cleaved form

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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