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3gt8

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[[Image:3gt8.png|left|200px]]
 
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{{STRUCTURE_3gt8| PDB=3gt8 | SCENE= }}
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==Crystal structure of the inactive EGFR kinase domain in complex with AMP-PNP==
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<StructureSection load='3gt8' size='340' side='right'caption='[[3gt8]], [[Resolution|resolution]] 2.96&Aring;' scene=''>
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===Crystal structure of the inactive EGFR kinase domain in complex with AMP-PNP===
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3gt8]] is a 5 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=3GT8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GT8 FirstGlance]. <br>
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{{ABSTRACT_PUBMED_19563760}}
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.955&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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==About this Structure==
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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=3gt8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gt8 OCA], [https://pdbe.org/3gt8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gt8 RCSB], [https://www.ebi.ac.uk/pdbsum/3gt8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gt8 ProSAT]</span></td></tr>
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[[3gt8]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GT8 OCA].
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</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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gt/3gt8_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3gt8 ConSurf].
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<div style="clear:both"></div>
==See Also==
==See Also==
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*[[Epidermal Growth Factor Receptor|Epidermal Growth Factor Receptor]]
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*[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019563760</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Receptor protein-tyrosine kinase]]
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[[Category: Large Structures]]
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[[Category: Das, R.]]
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[[Category: Das R]]
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[[Category: Deindl, S.]]
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[[Category: Deindl S]]
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[[Category: Endres, N F.]]
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[[Category: Endres NF]]
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[[Category: Engel, K.]]
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[[Category: Engel K]]
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[[Category: Jura, N.]]
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[[Category: Jura N]]
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[[Category: Kuriyan, J.]]
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[[Category: Kuriyan J]]
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[[Category: Lamers, M H.]]
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[[Category: Lamers MH]]
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[[Category: Wemmer, D E.]]
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[[Category: Wemmer DE]]
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[[Category: Zhang, X.]]
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[[Category: Zhang X]]
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[[Category: Anti-oncogene]]
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[[Category: Atp-binding]]
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[[Category: Cell cycle]]
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[[Category: Cell membrane]]
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[[Category: Dimer]]
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[[Category: Disease mutation]]
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[[Category: Disulfide bond]]
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[[Category: Glycoprotein]]
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[[Category: Inactive kinase]]
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[[Category: Isopeptide bond]]
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[[Category: Kinase]]
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[[Category: Membrane]]
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[[Category: Nucleotide-binding]]
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[[Category: Phosphoprotein]]
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[[Category: Receptor]]
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[[Category: Secreted]]
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[[Category: Transferase]]
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[[Category: Transmembrane]]
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[[Category: Tyrosine-protein kinase]]
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Current revision

Crystal structure of the inactive EGFR kinase domain in complex with AMP-PNP

PDB ID 3gt8

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