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7mph
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==GRB2 SH2 Domain with Compound 7== | |
| + | <StructureSection load='7mph' size='340' side='right'caption='[[7mph]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7mph]] is a 6 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=7MPH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MPH 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]] 2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZLY:(4-{(10R,11E,14S,18S)-18-(2-amino-2-oxoethyl)-14-[(naphthalen-1-yl)methyl]-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-10-yl}phenyl)acetic+acid'>ZLY</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=7mph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mph OCA], [https://pdbe.org/7mph PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mph RCSB], [https://www.ebi.ac.uk/pdbsum/7mph PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mph ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/GRB2_HUMAN GRB2_HUMAN] Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.<ref>PMID:1322798</ref> <ref>PMID:8178156</ref> <ref>PMID:19815557</ref> Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.<ref>PMID:1322798</ref> <ref>PMID:8178156</ref> <ref>PMID:19815557</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A monocarboxylic inhibitor was designed and synthesized to disrupt the protein-protein interaction (PPI) between GRB2 and phosphotyrosine-containing proteins. Biochemical characterizations show compound 7 binds with the Src homology 2 (SH2) domain of GRB2 and is more potent than EGFR1068 phosphopeptide 14-mer. X-ray crystallographic studies demonstrate compound 7 occupies the GRB2 binding site for phosphotyrosine-containing sequences and reveal key structural features for GRB2-inhibitor binding. This compound with a -1 formal charge offers a new direction for structural optimization to generate cell-permeable inhibitors for this key protein target of the aberrant Ras-MAPK signaling cascade. | ||
| - | + | Synthesis and structural characterization of a monocarboxylic inhibitor for GRB2 SH2 domain.,Xiao T, Sun L, Zhang M, Li Z, Haura EB, Schonbrunn E, Ji H Bioorg Med Chem Lett. 2021 Sep 7;51:128354. doi: 10.1016/j.bmcl.2021.128354. PMID:34506932<ref>PMID:34506932</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7mph" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Growth factor receptor-bound proteins 3D structures|Growth factor receptor-bound proteins 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Schonbrunn E]] | ||
| + | [[Category: Sun L]] | ||
Current revision
GRB2 SH2 Domain with Compound 7
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