This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
3ika
From Proteopedia
(Difference between revisions)
| (2 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| + | |||
==Crystal Structure of EGFR 696-1022 T790M Mutant Covalently Binding to WZ4002== | ==Crystal Structure of EGFR 696-1022 T790M Mutant Covalently Binding to WZ4002== | ||
| - | <StructureSection load='3ika' size='340' side='right' caption='[[3ika]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='3ika' size='340' side='right'caption='[[3ika]], [[Resolution|resolution]] 2.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3ika]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[3ika]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IKA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0UN:N-{3-[(5-CHLORO-2-{[2-METHOXY-4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-4-YL)OXY]PHENYL}PROP-2-ENAMIDE'>0UN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0UN:N-{3-[(5-CHLORO-2-{[2-METHOXY-4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-4-YL)OXY]PHENYL}PROP-2-ENAMIDE'>0UN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2jit|2jit]], [[2jiu|2jiu]], [[2jiv|2jiv]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2jit|2jit]], [[2jiu|2jiu]], [[2jiv|2jiv]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EGFR, ERBB1 ([ | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EGFR, ERBB1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://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'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ika FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ika OCA], [https://pdbe.org/3ika PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ika RCSB], [https://www.ebi.ac.uk/pdbsum/3ika PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ika ProSAT]</span></td></tr> |
</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> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ik/3ika_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ik/3ika_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | + | </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=3ika ConSurf]. |
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 31: | Line 32: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
| + | <div class="pdbe-citations 3ika" style="background-color:#fffaf0;"></div> | ||
==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: Human]] |
| + | [[Category: Large Structures]] | ||
[[Category: Receptor protein-tyrosine kinase]] | [[Category: Receptor protein-tyrosine kinase]] | ||
[[Category: Eck, M J]] | [[Category: Eck, M J]] | ||
[[Category: Yun, C H]] | [[Category: Yun, C H]] | ||
| + | [[Category: Alternative splicing]] | ||
[[Category: Atp-binding]] | [[Category: Atp-binding]] | ||
[[Category: Cell membrane]] | [[Category: Cell membrane]] | ||
| Line 53: | Line 57: | ||
[[Category: Nucleotide-binding]] | [[Category: Nucleotide-binding]] | ||
[[Category: Phosphoprotein]] | [[Category: Phosphoprotein]] | ||
| + | [[Category: Polymorphism]] | ||
[[Category: Receptor]] | [[Category: Receptor]] | ||
[[Category: Secreted]] | [[Category: Secreted]] | ||
| Line 60: | Line 65: | ||
[[Category: Tumor suppressor]] | [[Category: Tumor suppressor]] | ||
[[Category: Tyrosine-protein kinase]] | [[Category: Tyrosine-protein kinase]] | ||
| + | [[Category: Ubl conjugation]] | ||
[[Category: Wz-4002]] | [[Category: Wz-4002]] | ||
[[Category: Wz4002]] | [[Category: Wz4002]] | ||
Current revision
Crystal Structure of EGFR 696-1022 T790M Mutant Covalently Binding to WZ4002
| |||||||||||
Categories: Human | Large Structures | Receptor protein-tyrosine kinase | Eck, M J | Yun, C H | Alternative splicing | Atp-binding | Cell membrane | Disease mutation | Disulfide bond | Egfr | Glycoprotein | Isopeptide bond | Kinase | Membrane | Nucleotide-binding | Phosphoprotein | Polymorphism | Receptor | Secreted | T790m | Transferase | Transmembrane | Tumor suppressor | Tyrosine-protein kinase | Ubl conjugation | Wz-4002 | Wz4002
