5brr: Difference between revisions
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<StructureSection load='5brr' size='340' side='right'caption='[[5brr]], [[Resolution|resolution]] 3.16Å' scene=''> | <StructureSection load='5brr' size='340' side='right'caption='[[5brr]], [[Resolution|resolution]] 3.16Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5brr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BRR OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5brr]] 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=5BRR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BRR FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.16Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5brr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5brr OCA], [https://pdbe.org/5brr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5brr RCSB], [https://www.ebi.ac.uk/pdbsum/5brr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5brr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == 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 == | == 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> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Gong L]] | |||
[[Category: Gong | |||
Latest revision as of 06:53, 21 November 2024
Michaelis complex of tPA-S195A:PAI-1Michaelis complex of tPA-S195A:PAI-1
Structural highlights
DiseasePAI1_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. FunctionPAI1_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] Publication Abstract from PubMedThrombosis is a leading cause of death worldwide. Recombinant tissue-type plasminogen activator (tPA) is the FDA-approved thrombolytic drug. tPA is rapidly inactivated by endogenous plasminogen activators inhibitor-1 (PAI-1). Engineering on tPA to reduce its inhibition by PAI-1 without compromising its thrombolytic effect is a continuous effort. Precise details, with atomic resolution, of the molecular interactions between tPA and PAI-1 remains unknown despite extensive previous studies. Here, we report the crystal structure of tPA.PAI-1 Michaelis complex, which shows significant differences from the structure of its urokinase-type plasminogen activator (uPA) analogue, the uPA.PAI-1 Michaelis complex. The PAI-1 reactive center loop (RCL) adopts a unique kinked conformation, and the first 5 residues of RCL bends toward the beta-sheet A. The structure provides detailed interactions between tPA 37- and 60-loops with PAI-1. On the tPA side, the S2 and S1beta pockets opens up to accommodate PAI-1. This study lays down a foundation for understanding the specificity of PAI-1 for tPA, and provides structural clues to design newer generation of thrombolytic agents with reduced PAI-1 inactivation. Crystal Structure of the Michaelis Complex between Tissue-type Plasminogen Activator and Plasminogen Activators Inhibitor-1.,Gong L, Liu M, Zeng T, Shi X, Yuan C, Andreasen PA, Huang M J Biol Chem. 2015 Aug 31. pii: jbc.M115.677567. PMID:26324706[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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