4qqc: Difference between revisions
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==Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain in Complex with FIIN-2, an Irreversible Tyrosine Kinase Inhibitor Capable of Overcoming FGFR Kinase Gate-Keeper Mutations== | ==Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain in Complex with FIIN-2, an Irreversible Tyrosine Kinase Inhibitor Capable of Overcoming FGFR Kinase Gate-Keeper Mutations== | ||
<StructureSection load='4qqc' size='340' side='right' caption='[[4qqc]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='4qqc' size='340' side='right'caption='[[4qqc]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4qqc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QQC OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4qqc]] 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=4QQC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QQC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=37O:N-(4-{[3-(3,5-DIMETHOXYPHENYL)-7-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}-2-OXO-3,4-DIHYDROPYRIMIDO[4,5-D]PYRIMIDIN-1(2H)-YL]METHYL}PHENYL)PROPANAMIDE'>37O</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=37O:N-(4-{[3-(3,5-DIMETHOXYPHENYL)-7-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}-2-OXO-3,4-DIHYDROPYRIMIDO[4,5-D]PYRIMIDIN-1(2H)-YL]METHYL}PHENYL)PROPANAMIDE'>37O</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=4qqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qqc OCA], [https://pdbe.org/4qqc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qqc RCSB], [https://www.ebi.ac.uk/pdbsum/4qqc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qqc ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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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 4qqc" 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: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Huang Z]] | ||
[[Category: | [[Category: Mohammadi M]] | ||