7rct
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor RMC-4550== | |
| + | <StructureSection load='7rct' size='340' side='right'caption='[[7rct]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RCT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RCT 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]] 1.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4Q4:{3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-6-(2,3-dichlorophenyl)-5-methylpyrazin-2-yl}methanol'>4Q4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=7rct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rct OCA], [https://pdbe.org/7rct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rct RCSB], [https://www.ebi.ac.uk/pdbsum/7rct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rct ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | SHP2 is a protein tyrosine phosphatase that plays a critical role in the full activation of the Ras-MAPK pathway upon stimulation of receptor tyrosine kinases, which are frequently amplified or mutationally activated in human cancer. In addition, activating mutations in SHP2 result in developmental disorders and hematologic malignancies. Several allosteric inhibitors have been developed for SHP2 and are currently in clinical trials. Here, we report the development and evaluation of a SHP2 PROTAC created by conjugating RMC-4550 with pomalidomide using a PEG linker. This molecule is highly selective for SHP2, induces degradation of SHP2 in leukemic cells at submicromolar concentrations, inhibits MAPK signaling, and suppresses cancer cell growth. SHP2 PROTACs serve as an alternative strategy for targeting ERK-dependent cancers and are useful tools alongside allosteric inhibitors for dissecting the mechanisms by which SHP2 exerts its oncogenic activity. | ||
| - | + | Targeted Degradation of the Oncogenic Phosphatase SHP2.,Vemulapalli V, Donovan KA, Seegar TCM, Rogers JM, Bae M, Lumpkin RJ, Cao R, Henke MT, Ray SS, Fischer ES, Cuny GD, Blacklow SC Biochemistry. 2021 Aug 31;60(34):2593-2609. doi: 10.1021/acs.biochem.1c00377., Epub 2021 Aug 19. PMID:34411482<ref>PMID:34411482</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Seegar | + | <div class="pdbe-citations 7rct" style="background-color:#fffaf0;"></div> |
| + | |||
| + | ==See Also== | ||
| + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Seegar TCM]] | ||
Current revision
Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor RMC-4550
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