5y25: Difference between revisions
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The | ==EGFR kinase domain mutant (T790M/L858R) with covalent ligand NS-062== | ||
<StructureSection load='5y25' size='340' side='right' caption='[[5y25]], [[Resolution|resolution]] 3.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5y25]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y25 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y25 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8LU:(2R)-N-[4-[(3-chloranyl-4-fluoranyl-phenyl)amino]-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]-1-(2-fluoranylethanoyl)pyrrolidine-2-carboxamide'>8LU</scene></td></tr> | |||
[[Category: | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5y25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y25 OCA], [http://pdbe.org/5y25 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y25 RCSB], [http://www.ebi.ac.uk/pdbsum/5y25 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y25 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN]] Defects in EGFR are associated with lung cancer (LNCR) [MIM:[http://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 == | |||
[[http://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> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Receptor protein-tyrosine kinase]] | |||
[[Category: Abe, Y]] | |||
[[Category: Caaveiro, J M.M]] | |||
[[Category: Fuchida, H]] | |||
[[Category: Morimoto, S]] | |||
[[Category: Ojida, A]] | |||
[[Category: Sakamoto, S]] | |||
[[Category: Shindo, N]] | |||
[[Category: Shiroishi, M]] | |||
[[Category: Complex]] | |||
[[Category: Inhibitor]] | |||
[[Category: Transferase]] | |||
[[Category: Transferase-transferase inhibitor complex]] | |||
Revision as of 07:10, 25 July 2018
EGFR kinase domain mutant (T790M/L858R) with covalent ligand NS-062
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