4qqj - Revision history

OCA at 17:35, 20 September 2023

OCA — Wed, 20 Sep 2023 17:35:39 GMT

←Older revision		Revision as of 17:35, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4qqj]] 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=4QQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QQJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4qqj]] 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=4QQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QQJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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]] 1.682Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=4qqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqj OCA], [https://pdbe.org/4qqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qqj RCSB], [https://www.ebi.ac.uk/pdbsum/4qqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qqj 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=4qqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqj OCA], [https://pdbe.org/4qqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qqj RCSB], [https://www.ebi.ac.uk/pdbsum/4qqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qqj ProSAT]</span></td></tr>
	</table>		</table>

OCA at 13:47, 22 February 2023

OCA — Wed, 22 Feb 2023 13:47:10 GMT

←Older revision		Revision as of 13:47, 22 February 2023
Line 3:		Line 3:
	<StructureSection load='4qqj' size='340' side='right'caption='[[4qqj]], [[Resolution\|resolution]] 1.68Å' scene=''>		<StructureSection load='4qqj' size='340' side='right'caption='[[4qqj]], [[Resolution\|resolution]] 1.68Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qqj]] 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=4QQJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4QQJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qqj]] 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=4QQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QQJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qqc\|4qqc]], [[4qq5\|4qq5]], [[4qqt\|4qqt]]</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=4qqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqj OCA], [https://pdbe.org/4qqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qqj RCSB], [https://www.ebi.ac.uk/pdbsum/4qqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qqj ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FGFR4, JTK2, TKF ([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=4qqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqj OCA], [~~http~~://pdbe.org/4qqj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4qqj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4qqj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4qqj ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/FGFR4_HUMAN FGFR4_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.<ref>PMID:7680645</ref> <ref>PMID:7518429</ref> <ref>PMID:8663044</ref> <ref>PMID:11433297</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:18670643</ref> <ref>PMID:20683963</ref> <ref>PMID:20018895</ref> <ref>PMID:20798051</ref> <ref>PMID:21653700</ref> <ref>PMID:20876804</ref>	+	[https://www.uniprot.org/uniprot/FGFR4_HUMAN FGFR4_HUMAN] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.<ref>PMID:7680645</ref> <ref>PMID:7518429</ref> <ref>PMID:8663044</ref> <ref>PMID:11433297</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:18670643</ref> <ref>PMID:20683963</ref> <ref>PMID:20018895</ref> <ref>PMID:20798051</ref> <ref>PMID:21653700</ref> <ref>PMID:20876804</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Fibroblast growth factor receptor\|Fibroblast growth factor receptor]]	+	*[[Fibroblast growth factor receptor 3D receptor\|Fibroblast growth factor receptor 3D receptor]]
	== 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: Huang Z]]
-	[[Category: Huang, Z]]	+	[[Category: Mohammadi M]]
-	[[Category: Mohammadi, M]]	+
-	~~[[Category: Cell signaling]]~~	+
-	~~[[Category: Kinase domain fold]]~~	+
-	~~[[Category: Phosphotransferase]]~~	+
-	~~[[Category: Plasmamembrane]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 09:45, 24 April 2019

OCA — Wed, 24 Apr 2019 09:45:47 GMT

←Older revision		Revision as of 09:45, 24 April 2019
Line 1:		Line 1:

	==Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain Harboring the V550L Gate-Keeper Mutation==		==Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain Harboring the V550L Gate-Keeper Mutation==
-	<StructureSection load='4qqj' size='340' side='right' caption='[[4qqj]], [[Resolution\|resolution]] 1.68Å' scene=''>	+	<StructureSection load='4qqj' size='340' side='right'caption='[[4qqj]], [[Resolution\|resolution]] 1.68Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qqj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QQJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QQJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qqj]] 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=4QQJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QQJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qqc\|4qqc]], [[4qq5\|4qq5]], [[4qqt\|4qqt]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qqc\|4qqc]], [[4qq5\|4qq5]], [[4qqt\|4qqt]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FGFR4, JTK2, TKF ([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=4qqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqj OCA], [http://pdbe.org/4qqj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qqj RCSB], [http://www.ebi.ac.uk/pdbsum/4qqj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qqj 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=4qqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqj OCA], [http://pdbe.org/4qqj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qqj RCSB], [http://www.ebi.ac.uk/pdbsum/4qqj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qqj ProSAT]</span></td></tr>
Line 27:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Huang, Z]]		[[Category: Huang, Z]]

OCA at 13:15, 11 August 2016

OCA — Thu, 11 Aug 2016 13:15:28 GMT

←Older revision		Revision as of 13:15, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain Harboring the V550L Gate-Keeper Mutation==		==Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain Harboring the V550L Gate-Keeper Mutation==
	<StructureSection load='4qqj' size='340' side='right' caption='[[4qqj]], [[Resolution\|resolution]] 1.68Å' scene=''>		<StructureSection load='4qqj' size='340' side='right' caption='[[4qqj]], [[Resolution\|resolution]] 1.68Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qqc\|4qqc]], [[4qq5\|4qq5]], [[4qqt\|4qqt]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qqc\|4qqc]], [[4qq5\|4qq5]], [[4qqt\|4qqt]]</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=4qqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qqj RCSB], [http://www.ebi.ac.uk/pdbsum/4qqj 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=4qqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqj OCA], [http://pdbe.org/4qqj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qqj RCSB], [http://www.ebi.ac.uk/pdbsum/4qqj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qqj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4qqj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Fibroblast growth factor receptor\|Fibroblast growth factor receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:32, 25 December 2014

OCA — Thu, 25 Dec 2014 18:32:45 GMT

←Older revision		Revision as of 18:32, 25 December 2014
Line 8:		Line 8:
	<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=4qqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qqj RCSB], [http://www.ebi.ac.uk/pdbsum/4qqj 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=4qqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qqj RCSB], [http://www.ebi.ac.uk/pdbsum/4qqj PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FGFR4_HUMAN FGFR4_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.<ref>PMID:7680645</ref> <ref>PMID:7518429</ref> <ref>PMID:8663044</ref> <ref>PMID:11433297</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:18670643</ref> <ref>PMID:20683963</ref> <ref>PMID:20018895</ref> <ref>PMID:20798051</ref> <ref>PMID:21653700</ref> <ref>PMID:20876804</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Huang, Z.]]	+	[[Category: Huang, Z]]
-	[[Category: Mohammadi, M.]]	+	[[Category: Mohammadi, M]]
	[[Category: Cell signaling]]		[[Category: Cell signaling]]
	[[Category: Kinase domain fold]]		[[Category: Kinase domain fold]]

OCA at 11:22, 29 October 2014

OCA — Wed, 29 Oct 2014 11:22:31 GMT

←Older revision		Revision as of 11:22, 29 October 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain Harboring the V550L Gate-Keeper Mutation==
		+	<StructureSection load='4qqj' size='340' side='right' caption='[[4qqj]], [[Resolution\|resolution]] 1.68Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4qqj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QQJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QQJ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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">[[4qqc\|4qqc]], [[4qq5\|4qq5]], [[4qqt\|4qqt]]</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=4qqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qqj RCSB], [http://www.ebi.ac.uk/pdbsum/4qqj PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Drug-resistance acquisition through kinase gate-keeper mutations is a major hurdle in the clinic. Here, we determined the first crystal structures of the human FGFR4 kinase domain (FGFR4K) alone and complexed with ponatinib, a promiscuous type-2 (DFG-out) kinase inhibitor, and an oncogenic FGFR4K harboring the V550L gate-keeper mutation bound to FIIN-2, a new type-1 irreversible inhibitor. Remarkably, like ponatinib, FIIN-2 also binds in the DFG-out mode despite lacking a functional group necessary to occupy the pocket vacated upon the DFG-out flip. Structural analysis reveals that the covalent bond between FIIN-2 and a cysteine, uniquely present in the glycine-rich loop of FGFR kinases, facilitates the DFG-out conformation, which together with the internal flexibility of FIIN-2 enables FIIN-2 to avoid the steric clash with the gate-keeper mutation that causes the ponatinib resistance. The structural data provide a blueprint for the development of next generation anticancer inhibitors through combining the salient inhibitory mechanisms of ponatinib and FIIN-2.

-	~~The entry 4qqj is ON HOLD until Paper Publication~~	+	DFG-out Mode of Inhibition by an Irreversible Type-1 Inhibitor Capable of Overcoming Gate-Keeper Mutations in FGF Receptors.,Huang Z, Tan L, Wang H, Liu Y, Blais S, Deng J, Neubert TA, Gray NS, Li X, Mohammadi M ACS Chem Biol. 2014 Oct 27. PMID:25317566<ref>PMID:25317566</ref>

-	~~Authors~~: Huang, Z., Mohammadi, M.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Crystal Structure of FGF Receptor (FGFR) 4~~ Kinase ~~Domain Harboring the V550L Gate-Keeper Mutation~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Huang, Z.]]
		+	[[Category: Mohammadi, M.]]
		+	[[Category: Cell signaling]]
		+	[[Category: Kinase domain fold]]
		+	[[Category: Phosphotransferase]]
		+	[[Category: Plasmamembrane]]
		+	[[Category: Transferase]]

OCA at 08:14, 24 September 2014

OCA — Wed, 24 Sep 2014 08:14:12 GMT

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

	Authors: Huang, Z., Mohammadi, M.		Authors: Huang, Z., Mohammadi, M.

	Description: Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain Harboring the V550L Gate-Keeper Mutation		Description: Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain Harboring the V550L Gate-Keeper Mutation

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

OCA — Wed, 09 Jul 2014 06:52:39 GMT

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

←Older revision

Revision as of 06:52, 9 July 2014

OCA: New page: '''Unreleased structure''' The entry 4qqj is ON HOLD Authors: Huang, Z., Mohammadi, M. Description: Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain Harboring the V550L Gate-Ke...

OCA — Wed, 09 Jul 2014 06:52:38 GMT

New page: '''Unreleased structure''' The entry 4qqj is ON HOLD Authors: Huang, Z., Mohammadi, M. Description: Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain Harboring the V550L Gate-Ke...

New page

'''Unreleased structure'''

The entry 4qqj is ON HOLD

Authors: Huang, Z., Mohammadi, M.

Description: Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain Harboring the V550L Gate-Keeper Mutation