4g8o
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4g8o]] 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=4G8O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G8O FirstGlance]. <br> | <table><tr><td colspan='2'>[[4g8o]] 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=4G8O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G8O FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=96P:(2S)-3-({[3-(TRIFLUOROMETHYL)PHENOXY]CARBONYL}AMINO)PROPANE-1,2-DIYL+BIS(3,4,5-TRIHYDROXYBENZOATE)'>96P</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.71Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=96P:(2S)-3-({[3-(TRIFLUOROMETHYL)PHENOXY]CARBONYL}AMINO)PROPANE-1,2-DIYL+BIS(3,4,5-TRIHYDROXYBENZOATE)'>96P</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4g8o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g8o OCA], [https://pdbe.org/4g8o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g8o RCSB], [https://www.ebi.ac.uk/pdbsum/4g8o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g8o 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=4g8o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g8o OCA], [https://pdbe.org/4g8o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g8o RCSB], [https://www.ebi.ac.uk/pdbsum/4g8o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g8o ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== 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> | [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;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Plasminogen activator inhibitor type-1 (PAI-1) is a member of the serine protease inhibitor (serpin) family. Excessive PAI-1 activity is associated with human disease, making it an attractive pharmaceutical target. However, like other serpins, PAI-1 has a labile structure, making it a difficult target for the development of small molecule inhibitors, and to date, there are no US Food and Drug Administration-approved small molecule inactivators of any serpins. Here we describe the mechanistic and structural characterization of a high affinity inactivator of PAI-1. This molecule binds to PAI-1 reversibly and acts through an allosteric mechanism that inhibits PAI-1 binding to proteases and to its cofactor vitronectin. The binding site is identified by X-ray crystallography and mutagenesis as a pocket at the interface of beta-sheets B and C and alpha-helix H. A similar pocket is present on other serpins, suggesting that this site could be a common target in this structurally conserved protein family. | ||
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| - | Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1.,Li SH, Reinke AA, Sanders KL, Emal CD, Whisstock JC, Stuckey JA, Lawrence DA Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):E4941-9. doi:, 10.1073/pnas.1216499110. Epub 2013 Dec 2. PMID:24297881<ref>PMID:24297881</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4g8o" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Crystal Structure of a novel small molecule inactivator bound to plasminogen activator inhibitor-1
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