3lzb
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| - | {{STRUCTURE_3lzb| PDB=3lzb | SCENE= }} | ||
| - | ===EGFR kinase domain complexed with an imidazo[2,1-b]thiazole inhibitor=== | ||
| - | {{ABSTRACT_PUBMED_20346655}} | ||
| - | == | + | ==EGFR kinase domain complexed with an imidazo[2,1-b]thiazole inhibitor== |
| - | [[http://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN | + | <StructureSection load='3lzb' size='340' side='right'caption='[[3lzb]], [[Resolution|resolution]] 2.70Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3lzb]] is a 8 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=3LZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LZB 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]] 2.7Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ITI:N-[3-(5-{2-[(4-MORPHOLIN-4-YLPHENYL)AMINO]PYRIMIDIN-4-YL}IMIDAZO[2,1-B][1,3]THIAZOL-6-YL)PHENYL]-2-PHENYLACETAMIDE'>ITI</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=3lzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lzb OCA], [https://pdbe.org/3lzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lzb RCSB], [https://www.ebi.ac.uk/pdbsum/3lzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lzb ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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 == | ||
| + | [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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The design and enzyme activities of a novel class of imidazo[2,1-b]thiazoles is presented. | ||
| - | + | Imidazo[2,1-b]thiazoles: multitargeted inhibitors of both the insulin-like growth factor receptor and members of the epidermal growth factor family of receptor tyrosine kinases.,Fidanze SD, Erickson SA, Wang GT, Mantei R, Clark RF, Sorensen BK, Bamaung NY, Kovar P, Johnson EF, Swinger KK, Stewart KD, Zhang Q, Tucker LA, Pappano WN, Wilsbacher JL, Wang J, Sheppard GS, Bell RL, Davidsen SK, Hubbard RD Bioorg Med Chem Lett. 2010 Apr 15;20(8):2452-5. Epub 2010 Mar 7. PMID:20346655<ref>PMID:20346655</ref> | |
| - | [ | + | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 3lzb" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[Epidermal | + | *[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Swinger | + | [[Category: Swinger KK]] |
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Current revision
EGFR kinase domain complexed with an imidazo[2,1-b]thiazole inhibitor
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