5xfj
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of LY2874455 in complex of FGFR4 gatekeeper mutation (V550M)== | |
| - | + | <StructureSection load='5xfj' size='340' side='right' caption='[[5xfj]], [[Resolution|resolution]] 3.25Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[5xfj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XFJ FirstGlance]. <br> | |
| - | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6LF:2-[4-[E-2-[5-[(1R)-1-[3,5-BIS(CHLORANYL)PYRIDIN-4-YL]ETHOXY]-1H-INDAZOL-3-YL]ETHENYL]PYRAZOL-1-YL]ETHANOL'>6LF</scene></td></tr> | |
| - | [[Category: | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5xff|5xff]]</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=5xfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xfj OCA], [http://pdbe.org/5xfj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xfj RCSB], [http://www.ebi.ac.uk/pdbsum/5xfj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xfj 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> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Receptor protein-tyrosine kinase]] | ||
| + | [[Category: Chen, Y]] | ||
[[Category: Wu, D]] | [[Category: Wu, D]] | ||
| - | [[Category: | + | [[Category: Gatekeeper]] |
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Kinase]] | ||
| + | [[Category: Mutation]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 21:41, 9 August 2018
Crystal structure of LY2874455 in complex of FGFR4 gatekeeper mutation (V550M)
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