6jpj - Revision history

OCA at 10:18, 22 November 2023

OCA — Wed, 22 Nov 2023 10:18:09 GMT

←Older revision		Revision as of 10:18, 22 November 2023
Line 3:		Line 3:
	<StructureSection load='6jpj' size='340' side='right'caption='[[6jpj]], [[Resolution\|resolution]] 2.64Å' scene=''>		<StructureSection load='6jpj' size='340' side='right'caption='[[6jpj]], [[Resolution\|resolution]] 2.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6jpj]] 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=6JPJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6JPJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6jpj]] 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=6JPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JPJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FGF:N-[5-cyano-4-(2-methoxyethylamino)pyridin-2-yl]-7-methanoyl-6-[(4-methyl-2-oxidanylidene-piperazin-1-yl)methyl]-3,4-dihydro-2H-1,8-naphthyridine-1-carboxamide'>FGF</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]] 2.638Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FGF:N-[5-cyano-4-(2-methoxyethylamino)pyridin-2-yl]-7-methanoyl-6-[(4-methyl-2-oxidanylidene-piperazin-1-yl)methyl]-3,4-dihydro-2H-1,8-naphthyridine-1-carboxamide'>FGF</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6jpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jpj OCA], [https://pdbe.org/6jpj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jpj RCSB], [https://www.ebi.ac.uk/pdbsum/6jpj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jpj 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=6jpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jpj OCA], [~~http~~://pdbe.org/6jpj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6jpj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6jpj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6jpj 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 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6jpj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6jpj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[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: Chen X]]
-	[[Category: Chen, X]]	+	[[Category: Chen Y]]
-	[[Category: Chen, Y]]	+	[[Category: Zhou Z]]
-	[[Category: Zhou, Z]]	+
-	~~[[Category: Fgf401]]~~	+
-	~~[[Category: Fgfr4]]~~	+
-	~~[[Category: Reversible covalent inhibitor]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:31, 21 May 2019

OCA — Tue, 21 May 2019 07:31:07 GMT

←Older revision		Revision as of 07:31, 21 May 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6jpj is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of FGF401 in complex of FGFR4==
		+	<StructureSection load='6jpj' size='340' side='right'caption='[[6jpj]], [[Resolution\|resolution]] 2.64Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6jpj]] 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=6JPJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JPJ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FGF:N-[5-cyano-4-(2-methoxyethylamino)pyridin-2-yl]-7-methanoyl-6-[(4-methyl-2-oxidanylidene-piperazin-1-yl)methyl]-3,4-dihydro-2H-1,8-naphthyridine-1-carboxamide'>FGF</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6jpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jpj OCA], [http://pdbe.org/6jpj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jpj RCSB], [http://www.ebi.ac.uk/pdbsum/6jpj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jpj ProSAT]</span></td></tr>
		+	</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;">
		+	== Publication Abstract from PubMed ==
		+	Biochemical and structural studies provide information on the mode of action of FGF401 as a selective, reversible covalent inhibitor of FGFR4. Kinase and proliferation assays reveal that FGF401 has the ability to overcome gatekeeper mutations in FGFR4.

-	~~Authors: Zhou~~, Z., Chen, X., Chen, Y.	+	Characterization of FGF401 as a reversible covalent inhibitor of fibroblast growth factor receptor 4.,Zhou Z, Chen X, Fu Y, Zhang Y, Dai S, Li J, Chen L, Xu G, Chen Z, Chen Y Chem Commun (Camb). 2019 May 1. doi: 10.1039/c9cc02052g. PMID:31041948<ref>PMID:31041948</ref>

-	~~Description: Crystal structure~~ of ~~FGF401 in complex~~ of ~~FGFR4~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6jpj" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
		+	[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Chen, X]]		[[Category: Chen, X]]
-	[[Category: Zhou, Z]]
	[[Category: Chen, Y]]		[[Category: Chen, Y]]
		+	[[Category: Zhou, Z]]
		+	[[Category: Fgf401]]
		+	[[Category: Fgfr4]]
		+	[[Category: Reversible covalent inhibitor]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 05:20, 10 April 2019

OCA — Wed, 10 Apr 2019 05:20:51 GMT

←Older revision		Revision as of 05:20, 10 April 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6jpj is ON HOLD	+	The entry 6jpj is ON HOLD until Paper Publication

	Authors: Zhou, Z., Chen, X., Chen, Y.		Authors: Zhou, Z., Chen, X., Chen, Y.

OCA: Protected "6jpj" [edit=sysop:move=sysop]

OCA — Wed, 03 Apr 2019 04:28:15 GMT

Protected "6jpj" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:28, 3 April 2019

OCA: New page: '''Unreleased structure''' The entry 6jpj is ON HOLD Authors: Zhou, Z., Chen, X., Chen, Y. Description: Crystal structure of FGF401 in complex of FGFR4 [[Category: Unreleased Structure...

OCA — Wed, 03 Apr 2019 04:28:14 GMT

New page: '''Unreleased structure''' The entry 6jpj is ON HOLD Authors: Zhou, Z., Chen, X., Chen, Y. Description: Crystal structure of FGF401 in complex of FGFR4 [[Category: Unreleased Structure...

New page

'''Unreleased structure'''

The entry 6jpj is ON HOLD

Authors: Zhou, Z., Chen, X., Chen, Y.

Description: Crystal structure of FGF401 in complex of FGFR4
[[Category: Unreleased Structures]]
[[Category: Chen, X]]
[[Category: Zhou, Z]]
[[Category: Chen, Y]]