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6vh4
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6vh4 is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Wild type EGFR in complex with LN2380== | |
| + | <StructureSection load='6vh4' size='340' side='right'caption='[[6vh4]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VH4 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]] 2.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QQM:N-[3-({4-[4-(4-fluorophenyl)-2-(3-hydroxypropyl)-1H-imidazol-5-yl]pyridin-2-yl}amino)-4-methoxyphenyl]propanamide'>QQM</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=6vh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vh4 OCA], [https://pdbe.org/6vh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vh4 RCSB], [https://www.ebi.ac.uk/pdbsum/6vh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vh4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Acquired drug resistance in epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer is a persistent challenge in cancer therapy. Previous studies of trisubstituted imidazole inhibitors led to the serendipitous discovery of inhibitors that target the drug resistant EGFR(L858R/T790M/C797S) mutant with nanomolar potencies in a reversible binding mechanism. To dissect the molecular basis for their activity, we determined the binding modes of several trisubstituted imidazole inhibitors in complex with the EGFR kinase domain with X-ray crystallography. These structures reveal that the imidazole core acts as an H-bond acceptor for the catalytic lysine (K745) in the "alphaC-helix out" inactive state. Selective N-methylation of the H-bond accepting nitrogen ablates inhibitor potency, confirming the role of the K745 H-bond in potent, noncovalent inhibition of the C797S variant. Insights from these studies offer new strategies for developing next generation inhibitors targeting EGFR in non-small-cell lung cancer. | ||
| - | + | Structural Basis for EGFR Mutant Inhibition by Trisubstituted Imidazole Inhibitors.,Heppner DE, Gunther M, Wittlinger F, Laufer SA, Eck MJ J Med Chem. 2020 Apr 14. doi: 10.1021/acs.jmedchem.0c00200. PMID:32243152<ref>PMID:32243152</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6vh4" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Eck MJ]] | ||
| + | [[Category: Heppner DE]] | ||
Current revision
Wild type EGFR in complex with LN2380
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