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 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]] 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 id=' | + | <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> |
| - | + | ||
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [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> | ||
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</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]. | </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. | ||
| - | + | ==See Also== | |
| - | + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] | |
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== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[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
