1t4j
From Proteopedia
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==Allosteric Inhibition of Protein Tyrosine Phosphatase 1B== | ==Allosteric Inhibition of Protein Tyrosine Phosphatase 1B== | ||
| - | <StructureSection load='1t4j' size='340' side='right' caption='[[1t4j]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='1t4j' size='340' side='right'caption='[[1t4j]], [[Resolution|resolution]] 2.70Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1t4j]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1t4j]] is a 1 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=1T4J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T4J FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FRJ:3-(3,5-DIBROMO-4-HYDROXY-BENZOYL)-2-ETHYL-BENZOFURAN-6-SULFONIC+ACID+[4-(THIAZOL-2-YLSULFAMOYL)-PHENYL]-AMIDE'>FRJ</scene></td></tr> | |
| - | <tr><td class="sblockLbl"><b>[[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t4j OCA], [https://pdbe.org/1t4j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t4j RCSB], [https://www.ebi.ac.uk/pdbsum/1t4j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t4j ProSAT]</span></td></tr> |
| - | + | </table> | |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | == Function == |
| - | <table> | + | [https://www.uniprot.org/uniprot/PTN1_HUMAN PTN1_HUMAN] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.<ref>PMID:21135139</ref> <ref>PMID:22169477</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t4/1t4j_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t4/1t4j_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | + | </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=1t4j ConSurf]. |
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Obesity and type II diabetes are closely linked metabolic syndromes that afflict >100 million people worldwide. Although protein tyrosine phosphatase 1B (PTP1B) has emerged as a promising target for the treatment of both syndromes, the discovery of pharmaceutically acceptable inhibitors that bind at the active site remains a substantial challenge. Here we describe the discovery of an allosteric site in PTP1B. Crystal structures of PTP1B in complex with allosteric inhibitors reveal a novel site located approximately 20 A from the catalytic site. We show that allosteric inhibitors prevent formation of the active form of the enzyme by blocking mobility of the catalytic loop, thereby exploiting a general mechanism used by tyrosine phosphatases. Notably, these inhibitors exhibit selectivity for PTP1B and enhance insulin signaling in cells. Allosteric inhibition is a promising strategy for targeting PTP1B and constitutes a mechanism that may be applicable to other tyrosine phosphatases. | ||
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| - | Allosteric inhibition of protein tyrosine phosphatase 1B.,Wiesmann C, Barr KJ, Kung J, Zhu J, Erlanson DA, Shen W, Fahr BJ, Zhong M, Taylor L, Randal M, McDowell RS, Hansen SK Nat Struct Mol Biol. 2004 Aug;11(8):730-7. Epub 2004 Jul 18. PMID:15258570<ref>PMID:15258570</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
==See Also== | ==See Also== | ||
| - | *[[Tyrosine phosphatase|Tyrosine phosphatase]] | + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] |
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Barr | + | [[Category: Barr KJ]] |
| - | [[Category: Fahr | + | [[Category: Fahr BJ]] |
| - | [[Category: Hansen | + | [[Category: Hansen SK]] |
| - | [[Category: Kung | + | [[Category: Kung J]] |
| - | [[Category: McDowell | + | [[Category: McDowell RS]] |
| - | [[Category: Randal | + | [[Category: Randal M]] |
| - | [[Category: Shen | + | [[Category: Shen W]] |
| - | [[Category: Taylor | + | [[Category: Taylor L]] |
| - | [[Category: Wiesmann | + | [[Category: Wiesmann C]] |
| - | [[Category: Zhong | + | [[Category: Zhong M]] |
| - | [[Category: Zhu | + | [[Category: Zhu J]] |
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Current revision
Allosteric Inhibition of Protein Tyrosine Phosphatase 1B
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Categories: Homo sapiens | Large Structures | Barr KJ | Fahr BJ | Hansen SK | Kung J | McDowell RS | Randal M | Shen W | Taylor L | Wiesmann C | Zhong M | Zhu J
