3b2v: Difference between revisions

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-{{STRUCTURE_3b2v|  PDB=3b2v  |  SCENE=  }}
-===Crystal structure of the extracellular region of the epidermal growth factor receptor in complex with the Fab fragment of IMC-11F8===
-{{ABSTRACT_PUBMED_18275813}}
-==Disease==
+==Crystal structure of the extracellular region of the epidermal growth factor receptor in complex with the Fab fragment of IMC-11F8==
-[[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.
+<StructureSection load='3b2v' size='340' side='right'caption='[[3b2v]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3b2v]] is a 3 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=3B2V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3B2V 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]] 3.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=3b2v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b2v OCA], [https://pdbe.org/3b2v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3b2v RCSB], [https://www.ebi.ac.uk/pdbsum/3b2v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3b2v ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q6GMX6_HUMAN Q6GMX6_HUMAN]
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b2/3b2v_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=3b2v ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Therapeutic anticancer strategies that target and inactivate the epidermal growth factor receptor (EGFR) are under intense study in the clinic. Here we describe the mechanism of EGFR inhibition by an antibody drug IMC-11F8. IMC-11F8 is a fully human antibody that has similar antitumor potency as the chimeric cetuximab/Erbitux and might represent a safer therapeutic alternative. We report the X-ray crystal structure of the Fab fragment of IMC-11F8 (Fab11F8) in complex with the entire extracellular region and with isolated domain III of EGFR. We compare this to our previous study of the cetuximab/EGFR interaction. Fab11F8 interacts with a remarkably similar epitope, but through a completely different set of interactions. Both the similarities and differences in binding of these two antibodies have important implications for the development of inhibitors that could exploit this same mechanism of EGFR inhibition.
-==Function==
+Structural basis for EGF receptor inhibition by the therapeutic antibody IMC-11F8.,Li S, Kussie P, Ferguson KM Structure. 2008 Feb;16(2):216-27. PMID:18275813<ref>PMID:18275813</ref>
-[[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>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[3b2v]] is a 3 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=3B2V OCA].
+</div>
+<div class="pdbe-citations 3b2v" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Antibody|Antibody]]
+*[[Antibody 3D structures|Antibody 3D structures]]
-*[[Epidermal Growth Factor Receptor|Epidermal Growth Factor Receptor]]
+*[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]]
+*[[3D structures of human antibody|3D structures of human antibody]]
-==Reference==
+== References ==
-<ref group="xtra">PMID:018275813</ref><references group="xtra"/><references/>
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Receptor protein-tyrosine kinase]]
+[[Category: Large Structures]]
-[[Category: Ferguson, K M.]]
+[[Category: Ferguson KM]]
-[[Category: Kussie, P.]]
+[[Category: Kussie P]]
-[[Category: Li, S.]]
+[[Category: Li S]]
-[[Category: Anti-oncogene]]
-[[Category: Antigen:antibody complex]]
-[[Category: Antitumor]]
-[[Category: Atp-binding]]
-[[Category: Cell cycle]]
-[[Category: Cell surface receptor]]
-[[Category: Disease mutation]]
-[[Category: Drug]]
-[[Category: Fab fragment]]
-[[Category: Glycoprotein]]
-[[Category: Immune system-transferase complex]]
-[[Category: Kinase]]
-[[Category: Membrane]]
-[[Category: Nucleotide-binding]]
-[[Category: Phosphoprotein]]
-[[Category: Secreted]]
-[[Category: Transferase]]
-[[Category: Transmembrane]]
-[[Category: Tyrosine-protein kinase]]