7v29 - Revision history

OCA at 17:19, 29 November 2023

OCA — Wed, 29 Nov 2023 17:19:22 GMT

←Older revision		Revision as of 17:19, 29 November 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7v29]] is a 2 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=7V29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V29 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7v29]] is a 2 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=7V29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V29 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5JR:N-[2-[[3-(3,5-dimethoxyphenyl)-2-oxidanylidene-1-[3-(4-propanoylpiperazin-1-yl)propyl]-4H-pyrimido[4,5-d]pyrimidin-7-yl]amino]phenyl]propanamide'>5JR</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]] 1.983Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5JR:N-[2-[[3-(3,5-dimethoxyphenyl)-2-oxidanylidene-1-[3-(4-propanoylpiperazin-1-yl)propyl]-4H-pyrimido[4,5-d]pyrimidin-7-yl]amino]phenyl]propanamide'>5JR</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=7v29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v29 OCA], [https://pdbe.org/7v29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v29 RCSB], [https://www.ebi.ac.uk/pdbsum/7v29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v29 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=7v29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v29 OCA], [https://pdbe.org/7v29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v29 RCSB], [https://www.ebi.ac.uk/pdbsum/7v29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v29 ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 7v29" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7v29" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Fibroblast growth factor receptor 3D receptor\|Fibroblast growth factor receptor 3D receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:58, 8 February 2023

OCA — Wed, 08 Feb 2023 06:58:15 GMT

←Older revision		Revision as of 06:58, 8 February 2023
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	==Crystal structure of FGFR4 with a dual-warhead covalent inhhibitor==		==Crystal structure of FGFR4 with a dual-warhead covalent inhhibitor==
-	<StructureSection load='7v29' size='340' side='right'caption='[[7v29]]' scene=''>	+	<StructureSection load='7v29' size='340' side='right'caption='[[7v29]], [[Resolution\|resolution]] 1.98Å' 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=7V29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V29 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7v29]] is a 2 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=7V29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V29 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=7v29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v29 OCA], [https://pdbe.org/7v29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v29 RCSB], [https://www.ebi.ac.uk/pdbsum/7v29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v29 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=5JR:N-[2-[[3-(3,5-dimethoxyphenyl)-2-oxidanylidene-1-[3-(4-propanoylpiperazin-1-yl)propyl]-4H-pyrimido[4,5-d]pyrimidin-7-yl]amino]phenyl]propanamide'>5JR</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=7v29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v29 OCA], [https://pdbe.org/7v29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v29 RCSB], [https://www.ebi.ac.uk/pdbsum/7v29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v29 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[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;">
		+	== Publication Abstract from PubMed ==
		+	The fibroblast growth factor 19 (FGF19)/fibroblast growth factor receptor 4 (FGFR4) signaling pathways play critical roles in a variety of cancers, such as hepatocellular carcinoma (HCC). FGFR4 is recognized as a promising target to treat HCC. Currently, all FGFR covalent inhibitors target one of the two cysteines (Cys477 and Cys552). Here, we designed and synthesized a dual-warhead covalent FGFR4 inhibitor, CXF-009, targeting Cys477 and Cys552 of FGFR4. We report the cocrystal structure of FGFR4 with CXF-009, which exhibits a dual-warhead covalent binding mode. CXF-009 exhibited stronger selectivity for FGFR4 than FGFR1-3 and other kinases. CXF-009 can also potently inhibit the single cystine mutants, FGFR4(C477A) and FGFR4(C552A), of FGFR4. In summary, our study provides a dual-warhead covalent FGFR4 inhibitor that can covalently target two cysteines of FGFR4. CXF-009, to our knowledge, is the first reported inhibitor that forms dual-warhead covalent bonds with two cysteine residues in FGFR4. CXF-009 also has the potential to overcome drug induced resistant FGFR4 mutations and might serve as a lead compound for future anticancer drug discovery.
		+
		+	Structure-based design of a dual-warhead covalent inhibitor of FGFR4.,Chen X, Li H, Lin Q, Dai S, Yue S, Qu L, Li M, Guo M, Wei H, Li J, Jiang L, Xu G, Chen Y Commun Chem. 2022 Mar 17;5(1):36. doi: 10.1038/s42004-022-00657-9. PMID:36697897<ref>PMID:36697897</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7v29" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Chen XJ]]		[[Category: Chen XJ]]

OCA at 10:48, 30 March 2022

OCA — Wed, 30 Mar 2022 10:48:46 GMT

←Older revision		Revision as of 10:48, 30 March 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7v29 is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of FGFR4 with a dual-warhead covalent inhhibitor==
-		+	<StructureSection load='7v29' size='340' side='right'caption='[[7v29]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7V29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V29 FirstGlance]. <br>
-	~~Description~~:	+	</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=7v29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v29 OCA], [https://pdbe.org/7v29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v29 RCSB], [https://www.ebi.ac.uk/pdbsum/7v29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v29 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Chen XJ]]
		+	[[Category: Chen YH]]
		+	[[Category: Dai SY]]
		+	[[Category: Jiang LY]]
		+	[[Category: Qu LZ]]

OCA at 07:54, 8 September 2021

OCA — Wed, 08 Sep 2021 07:54:37 GMT

←Older revision		Revision as of 07:54, 8 September 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7v29 is ON HOLD	+	The entry 7v29 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7v29" [edit=sysop:move=sysop]

OCA — Wed, 18 Aug 2021 05:13:20 GMT

Protected "7v29" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:13, 18 August 2021

OCA: New page: '''Unreleased structure''' The entry 7v29 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 18 Aug 2021 05:13:19 GMT

New page: '''Unreleased structure''' The entry 7v29 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7v29 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]