1oc0

From Proteopedia

(Difference between revisions)

Revision as of 06:42, 7 August 2019

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

Structural highlights

1oc0 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1a7c, 1b3k, 1c5g, 1db2, 1dvm, 1dvn, 1lj5, 9pai
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] [VTNC_HUMAN] Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway. Somatomedin-B is a growth hormone-dependent serum factor with protease-inhibiting activity.

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.

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
↑ 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

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/1oc0"

@@ Line 1: / Line 1: @@
 ==plasminogen activator inhibitor-1 complex with somatomedin B domain of vitronectin==
-<StructureSection load='1oc0' size='340' side='right' caption='[[1oc0]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
+<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 [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OC0 FirstGlance]. <br>
@@ Line 15: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oc/1oc0_consurf.spt"</scriptWhenChecked>
+    <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/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 30: / Line 30: @@
 </div>
 <div class="pdbe-citations 1oc0" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Plasminogen activator inhibitor|Plasminogen activator inhibitor]]
 == References ==
 <references/>
@@ Line 35: / Line 38: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Carrell, R W]]
 [[Category: Huntington, J A]]

1oc0

From Proteopedia

Revision as of 06:42, 7 August 2019

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

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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