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4i24
From Proteopedia
(Difference between revisions)
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==Structure of T790M EGFR kinase domain co-crystallized with dacomitinib== | ==Structure of T790M EGFR kinase domain co-crystallized with dacomitinib== | ||
| - | <StructureSection load='4i24' size='340' side='right' caption='[[4i24]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4i24' size='340' side='right'caption='[[4i24]], [[Resolution|resolution]] 1.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4i24]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[4i24]] is a 2 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=4I24 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I24 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1C9:(2E)-N-{4-[(3-CHLORO-4-FLUOROPHENYL)AMINO]-7-METHOXYQUINAZOLIN-6-YL}-4-(PIPERIDIN-1-YL)BUT-2-ENAMIDE'>1C9</scene | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1C9:(2E)-N-{4-[(3-CHLORO-4-FLUOROPHENYL)AMINO]-7-METHOXYQUINAZOLIN-6-YL}-4-(PIPERIDIN-1-YL)BUT-2-ENAMIDE'>1C9</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=4i24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i24 OCA], [https://pdbe.org/4i24 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i24 RCSB], [https://www.ebi.ac.uk/pdbsum/4i24 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i24 ProSAT]</span></td></tr> | |
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [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. |
== Function == | == Function == | ||
| - | [ | + | [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> |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
| - | *[[Epidermal | + | *[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]] |
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Brodsky | + | [[Category: Brodsky O]] |
| - | [[Category: Feng | + | [[Category: Feng J]] |
| - | [[Category: Ferre | + | [[Category: Ferre R]] |
| - | [[Category: Gajiwala | + | [[Category: Gajiwala KS]] |
| - | [[Category: Ryan | + | [[Category: Ryan K]] |
| - | [[Category: Stewart | + | [[Category: Stewart A]] |
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Current revision
Structure of T790M EGFR kinase domain co-crystallized with dacomitinib
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Categories: Homo sapiens | Large Structures | Brodsky O | Feng J | Ferre R | Gajiwala KS | Ryan K | Stewart A
