View source for 8skl


==PTP1B in complex with 182==
<StructureSection load='8skl' size='340' side='right'caption='[[8skl]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8skl]] 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=8SKL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SKL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=V2O:5-[1-fluoranyl-7-(3-methyl-3-oxidanyl-butoxy)-3-oxidanyl-naphthalen-2-yl]-1,1-bis(oxidanylidene)-1,2,5-thiadiazolidin-3-one'>V2O</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=8skl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8skl OCA], [https://pdbe.org/8skl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8skl RCSB], [https://www.ebi.ac.uk/pdbsum/8skl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8skl ProSAT]</span></td></tr>
</table>
== 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The inhibition of protein tyrosine phosphatases 1B (PTP1B) and N2 (PTPN2) has emerged as an exciting approach for bolstering T cell anti-tumor immunity. ABBV-CLS-484 is a PTP1B/PTPN2 inhibitor in clinical trials for solid tumors. Here we have explored the therapeutic potential of a related small-molecule-inhibitor, Compound-182. We demonstrate that Compound-182 is a highly potent and selective active site competitive inhibitor of PTP1B and PTPN2 that enhances T cell recruitment and activation and represses the growth of tumors in mice, without promoting overt immune-related toxicities. The enhanced anti-tumor immunity in immunogenic tumors can be ascribed to the inhibition of PTP1B/PTPN2 in T cells, whereas in cold tumors, Compound-182 elicited direct effects on both tumor cells and T cells. Importantly, treatment with Compound-182 rendered otherwise resistant tumors sensitive to alpha-PD-1 therapy. Our findings establish the potential for small molecule inhibitors of PTP1B and PTPN2 to enhance anti-tumor immunity and combat cancer.

A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity.,Liang S, Tran E, Du X, Dong J, Sudholz H, Chen H, Qu Z, Huntington ND, Babon JJ, Kershaw NJ, Zhang ZY, Baell JB, Wiede F, Tiganis T Nat Commun. 2023 Jul 27;14(1):4524. doi: 10.1038/s41467-023-40170-8. PMID:37500611<ref>PMID:37500611</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8skl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Babon JJ]]
[[Category: Chen H]]
[[Category: Kershaw NJ]]
[[Category: Tiganis T]]