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.


7ltx

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
==EGFR (T790M/V948R) in complex with quinazolinone allosteric inhibitor==
==EGFR (T790M/V948R) in complex with quinazolinone allosteric inhibitor==
-
<StructureSection load='7ltx' size='340' side='right'caption='[[7ltx]]' scene=''>
+
<StructureSection load='7ltx' size='340' side='right'caption='[[7ltx]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LTX FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[7ltx]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LTX FirstGlance]. <br>
-
</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=7ltx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ltx OCA], [https://pdbe.org/7ltx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ltx RCSB], [https://www.ebi.ac.uk/pdbsum/7ltx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ltx ProSAT]</span></td></tr>
+
</td></tr><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>, <scene name='pdbligand=YFA:(2R)-2-{5-fluoro-6-[4-(1-methylpiperidin-4-yl)phenyl]-4-oxoquinazolin-3(4H)-yl}-2-phenyl-N-(1,3-thiazol-2-yl)acetamide'>YFA</scene></td></tr>
 +
<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'>[https://proteopedia.org/fgij/fg.htm?mol=7ltx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ltx OCA], [https://pdbe.org/7ltx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ltx RCSB], [https://www.ebi.ac.uk/pdbsum/7ltx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ltx ProSAT]</span></td></tr>
</table>
</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>
 +
== References ==
 +
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Beyett TS]]
+
[[Category: Receptor protein-tyrosine kinase]]
-
[[Category: Eck MJ]]
+
[[Category: Beyett, T S]]
 +
[[Category: Eck, M J]]
 +
[[Category: Allosteric]]
 +
[[Category: Egfr]]
 +
[[Category: Inhibitor]]
 +
[[Category: Kinase]]
 +
[[Category: Quinazolinone]]
 +
[[Category: Transferase]]
 +
[[Category: Transferase-inhibitor complex]]

Revision as of 10:19, 13 April 2022

EGFR (T790M/V948R) in complex with quinazolinone allosteric inhibitor

PDB ID 7ltx

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7ltx"
Personal tools