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7k1h

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==EGFR L858R/V948R in complex with osimertinib and allosteric inhibitor JBJ-09-063==
==EGFR L858R/V948R in complex with osimertinib and allosteric inhibitor JBJ-09-063==
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<StructureSection load='7k1h' size='340' side='right'caption='[[7k1h]]' scene=''>
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<StructureSection load='7k1h' size='340' side='right'caption='[[7k1h]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K1H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K1H FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7k1h]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K1H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K1H FirstGlance]. <br>
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</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=7k1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k1h OCA], [https://pdbe.org/7k1h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k1h RCSB], [https://www.ebi.ac.uk/pdbsum/7k1h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k1h ProSAT]</span></td></tr>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VNS:(2R)-2-(5-fluoro-2-hydroxyphenyl)-2-{6-[4-(1-methylpiperidin-4-yl)phenyl]-1-oxo-1,3-dihydro-2H-isoindol-2-yl}-N-(1,3-thiazol-2-yl)acetamide'>VNS</scene>, <scene name='pdbligand=YY3:N-(2-{[2-(DIMETHYLAMINO)ETHYL](METHYL)AMINO}-4-METHOXY-5-{[4-(1-METHYL-1H-INDOL-3-YL)PYRIMIDIN-2-YL]AMINO}PHENYL)PROP-2-ENAMIDE'>YY3</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7k1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k1h OCA], [https://pdbe.org/7k1h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k1h RCSB], [https://www.ebi.ac.uk/pdbsum/7k1h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k1h ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[[https://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN]] Defects in EGFR are associated with lung cancer (LNCR) [MIM:[https://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.
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== Function ==
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[[https://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN]] Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref> Isoform 2 may act as an antagonist of EGF action.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Beyett TS]]
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[[Category: Receptor protein-tyrosine kinase]]
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[[Category: Eck MJ]]
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[[Category: Beyett, T S]]
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[[Category: Eck, M J]]
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[[Category: Allosteric]]
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[[Category: Egfr]]
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[[Category: Inhibitor]]
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[[Category: Kinase]]
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[[Category: Transferase]]
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[[Category: Transferase-transferase inhibitor complex]]

Revision as of 10:22, 18 May 2022

EGFR L858R/V948R in complex with osimertinib and allosteric inhibitor JBJ-09-063

PDB ID 7k1h

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