4rj8 - Revision history

OCA at 17:50, 20 September 2023

OCA — Wed, 20 Sep 2023 17:50:49 GMT

←Older revision		Revision as of 17:50, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rj8]] is a 1 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=4RJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RJ8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rj8]] is a 1 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=4RJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RJ8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3QS:1-CYCLOPENTYL-N-[2-(4-METHOXYPIPERIDIN-1-YL)PYRIMIDIN-4-YL]-1H-PYRROLO[3,2-C]PYRIDIN-6-AMINE'>3QS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3QS:1-CYCLOPENTYL-N-[2-(4-METHOXYPIPERIDIN-1-YL)PYRIMIDIN-4-YL]-1H-PYRROLO[3,2-C]PYRIDIN-6-AMINE'>3QS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4rj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rj8 OCA], [https://pdbe.org/4rj8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rj8 RCSB], [https://www.ebi.ac.uk/pdbsum/4rj8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rj8 ProSAT]</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=4rj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rj8 OCA], [https://pdbe.org/4rj8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rj8 RCSB], [https://www.ebi.ac.uk/pdbsum/4rj8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rj8 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:59, 2 March 2023

OCA — Thu, 02 Mar 2023 06:59:09 GMT

←Older revision		Revision as of 06:59, 2 March 2023
Line 3:		Line 3:
	<StructureSection load='4rj8' size='340' side='right'caption='[[4rj8]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4rj8' size='340' side='right'caption='[[4rj8]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rj8]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RJ8 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4RJ8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rj8]] is a 1 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=4RJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RJ8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3QS:1-CYCLOPENTYL-N-[2-(4-METHOXYPIPERIDIN-1-YL)PYRIMIDIN-4-YL]-1H-PYRROLO[3,2-C]PYRIDIN-6-AMINE'>3QS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3QS:1-CYCLOPENTYL-N-[2-(4-METHOXYPIPERIDIN-1-YL)PYRIMIDIN-4-YL]-1H-PYRROLO[3,2-C]PYRIDIN-6-AMINE'>3QS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rj3\|4rj3]], [[4rj4\|4rj4]], [[4rj5\|4rj5]], [[4rj6\|4rj6]], [[4rj7\|4rj7]]</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=4rj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rj8 OCA], [https://pdbe.org/4rj8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rj8 RCSB], [https://www.ebi.ac.uk/pdbsum/4rj8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rj8 ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EGFR, ERBB, ERBB1, HER1 ([http://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'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4rj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rj8 OCA], [~~http~~://pdbe.org/4rj8 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4rj8 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4rj8 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4rj8 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[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.	+	[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 ==
-	[~~[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>	+	[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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:

	==See Also==		==See Also==
-	*[[Epidermal ~~Growth Factor Receptor~~\|Epidermal ~~Growth Factor Receptor~~]]	+	*[[Epidermal growth factor receptor 3D structures\|Epidermal growth factor receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Eigenbrot C]]
-	[[Category: Eigenbrot, C]]	+	[[Category: Yu C]]
-	[[Category: Yu, C]]	+
-	~~[[Category: Phosphotransfer catalyst]]~~	+
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 10:01, 1 May 2019

OCA — Wed, 01 May 2019 10:01:40 GMT

←Older revision		Revision as of 10:01, 1 May 2019
Line 1:		Line 1:

	==EGFR kinase (T790M/L858R) with inhibitor compound 8==		==EGFR kinase (T790M/L858R) with inhibitor compound 8==
-	<StructureSection load='4rj8' size='340' side='right' caption='[[4rj8]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='4rj8' size='340' side='right'caption='[[4rj8]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rj8]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RJ8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rj8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RJ8 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3QS:1-CYCLOPENTYL-N-[2-(4-METHOXYPIPERIDIN-1-YL)PYRIMIDIN-4-YL]-1H-PYRROLO[3,2-C]PYRIDIN-6-AMINE'>3QS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3QS:1-CYCLOPENTYL-N-[2-(4-METHOXYPIPERIDIN-1-YL)PYRIMIDIN-4-YL]-1H-PYRROLO[3,2-C]PYRIDIN-6-AMINE'>3QS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rj3\|4rj3]], [[4rj4\|4rj4]], [[4rj5\|4rj5]], [[4rj6\|4rj6]], [[4rj7\|4rj7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rj3\|4rj3]], [[4rj4\|4rj4]], [[4rj5\|4rj5]], [[4rj6\|4rj6]], [[4rj7\|4rj7]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EGFR, ERBB, ERBB1, HER1 ([http://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'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rj8 OCA], [http://pdbe.org/4rj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rj8 RCSB], [http://www.ebi.ac.uk/pdbsum/4rj8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rj8 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rj8 OCA], [http://pdbe.org/4rj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rj8 RCSB], [http://www.ebi.ac.uk/pdbsum/4rj8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rj8 ProSAT]</span></td></tr>
Line 29:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Eigenbrot, C]]		[[Category: Eigenbrot, C]]

OCA at 11:00, 11 August 2016

OCA — Thu, 11 Aug 2016 11:00:33 GMT

←Older revision		Revision as of 11:00, 11 August 2016
Line 1:		Line 1:
		+
	==EGFR kinase (T790M/L858R) with inhibitor compound 8==		==EGFR kinase (T790M/L858R) with inhibitor compound 8==
	<StructureSection load='4rj8' size='340' side='right' caption='[[4rj8]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4rj8' size='340' side='right' caption='[[4rj8]], [[Resolution\|resolution]] 2.50Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rj3\|4rj3]], [[4rj4\|4rj4]], [[4rj5\|4rj5]], [[4rj6\|4rj6]], [[4rj7\|4rj7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rj3\|4rj3]], [[4rj4\|4rj4]], [[4rj5\|4rj5]], [[4rj6\|4rj6]], [[4rj7\|4rj7]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rj8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rj8 RCSB], [http://www.ebi.ac.uk/pdbsum/4rj8 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rj8 OCA], [http://pdbe.org/4rj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rj8 RCSB], [http://www.ebi.ac.uk/pdbsum/4rj8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rj8 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 4rj8" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Epidermal Growth Factor Receptor\|Epidermal Growth Factor Receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:55, 26 November 2014

OCA — Wed, 26 Nov 2014 07:55:39 GMT

←Older revision		Revision as of 07:55, 26 November 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==EGFR kinase (T790M/L858R) with inhibitor compound 8==
		+	<StructureSection load='4rj8' size='340' side='right' caption='[[4rj8]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4rj8]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RJ8 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3QS:1-CYCLOPENTYL-N-[2-(4-METHOXYPIPERIDIN-1-YL)PYRIMIDIN-4-YL]-1H-PYRROLO[3,2-C]PYRIDIN-6-AMINE'>3QS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rj3\|4rj3]], [[4rj4\|4rj4]], [[4rj5\|4rj5]], [[4rj6\|4rj6]], [[4rj7\|4rj7]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rj8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rj8 RCSB], [http://www.ebi.ac.uk/pdbsum/4rj8 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[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.
		+	== Function ==
		+	[[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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Activating mutations within the epidermal growth factor receptor (EGFR) kinase domain, commonly L858R or deletions within exon 19, increase EGFR-driven cell proliferation and survival and are correlated with impressive responses to the EGFR inhibitors erlotinib and gefitinib in nonsmall cell lung cancer patients. Approximately 60% of acquired resistance to these agents is driven by a single secondary mutation within the EGFR kinase domain, specifically substitution of the gatekeeper residue threonine-790 with methionine (T790M). Due to dose-limiting toxicities associated with inhibition of wild-type EGFR (wtEGFR), we sought inhibitors of T790M-containing EGFR mutants with selectivity over wtEGFR. We describe the evolution of HTS hits derived from Jak2/Tyk2 inhibitors into selective EGFR inhibitors. X-ray crystal structures revealed two distinct binding modes and enabled the design of a selective series of novel diaminopyrimidine-based inhibitors with good potency against T790M-containing mutants of EGFR, high selectivity over wtEGFR, broad kinase selectivity, and desirable physicochemical properties.

-	~~The entry 4rj8 is ON HOLD until Paper Publication~~	+	Discovery of Selective and Noncovalent Diaminopyrimidine-Based Inhibitors of Epidermal Growth Factor Receptor Containing the T790M Resistance Mutation.,Hanan EJ, Eigenbrot C, Bryan MC, Burdick DJ, Chan BK, Chen Y, Dotson J, Heald RA, Jackson PS, La H, Lainchbury MD, Malek S, Purkey HE, Schaefer G, Schmidt S, Seward EM, Sideris S, Tam C, Wang S, Yeap SK, Yen I, Yin J, Yu C, Zilberleyb I, Heffron TP J Med Chem. 2014 Nov 20. PMID:25383627<ref>PMID:25383627</ref>

-	~~Authors~~: Eigenbrot, C., Yu, C.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~EGFR~~ kinase ~~(T790M/L858R) with~~ inhibitor ~~compound 8~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Eigenbrot, C]]
		+	[[Category: Yu, C]]
		+	[[Category: Phosphotransfer catalyst]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 09:43, 22 October 2014

OCA — Wed, 22 Oct 2014 09:43:00 GMT

←Older revision		Revision as of 09:43, 22 October 2014
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4rj8 is ON HOLD	+	The entry 4rj8 is ON HOLD until Paper Publication

	Authors: Eigenbrot, C., Yu, C.		Authors: Eigenbrot, C., Yu, C.

-	Description: EGFR kinase (T790M/L858R) with ~~inhibit~~ compound 8	+	Description: EGFR kinase (T790M/L858R) with inhibitor compound 8

OCA: Protected "4rj8" [edit=sysop:move=sysop]

OCA — Mon, 20 Oct 2014 09:31:20 GMT

Protected "4rj8" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:31, 20 October 2014

OCA: New page: '''Unreleased structure''' The entry 4rj8 is ON HOLD Authors: Eigenbrot, C., Yu, C. Description: EGFR kinase (T790M/L858R) with inhibit compound 8

OCA — Mon, 20 Oct 2014 09:31:19 GMT

New page: '''Unreleased structure''' The entry 4rj8 is ON HOLD Authors: Eigenbrot, C., Yu, C. Description: EGFR kinase (T790M/L858R) with inhibit compound 8

New page

'''Unreleased structure'''

The entry 4rj8 is ON HOLD

Authors: Eigenbrot, C., Yu, C.

Description: EGFR kinase (T790M/L858R) with inhibit compound 8