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| | <StructureSection load='1pwa' size='340' side='right'caption='[[1pwa]], [[Resolution|resolution]] 1.30Å' scene=''> | | <StructureSection load='1pwa' size='340' side='right'caption='[[1pwa]], [[Resolution|resolution]] 1.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1pwa]] 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=1PWA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1PWA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1pwa]] 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=1PWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PWA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 1.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FGF19 ([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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1pwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pwa OCA], [http://pdbe.org/1pwa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pwa RCSB], [http://www.ebi.ac.uk/pdbsum/1pwa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1pwa 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=1pwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pwa OCA], [https://pdbe.org/1pwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pwa RCSB], [https://www.ebi.ac.uk/pdbsum/1pwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pwa ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FGF19_HUMAN FGF19_HUMAN]] Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. Stimulates glucose uptake in adipocytes. Activity requires the presence of KLB and FGFR4.<ref>PMID:12815072</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:19085950</ref> | + | [https://www.uniprot.org/uniprot/FGF19_HUMAN FGF19_HUMAN] Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. Stimulates glucose uptake in adipocytes. Activity requires the presence of KLB and FGFR4.<ref>PMID:12815072</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:19085950</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Blundell, T L]] | + | [[Category: Blundell TL]] |
| - | [[Category: Chirgadze, D]] | + | [[Category: Chirgadze D]] |
| - | [[Category: Fernandez-Recio, J]] | + | [[Category: Fernandez-Recio J]] |
| - | [[Category: Harmer, N J]] | + | [[Category: Harmer NJ]] |
| - | [[Category: Pellegrini, L]] | + | [[Category: Pellegrini L]] |
| - | [[Category: Beta trefoil]]
| + | |
| - | [[Category: Disulphide bond]]
| + | |
| - | [[Category: Hormone-growth factor complex]]
| + | |
| Structural highlights
Function
FGF19_HUMAN Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. Stimulates glucose uptake in adipocytes. Activity requires the presence of KLB and FGFR4.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The 22 members of the FGF family have been implicated in cell proliferation, differentiation, survival, and migration. They are required for both development and maintenance of vertebrates, demonstrating an exquisite pattern of affinities for both protein and proteoglycan receptors. FGF19, one of the most divergent human FGFs, is unique in binding solely to one receptor, FGFR4. We have used molecular replacement to solve the crystal structure of FGF19 at 1.3 A resolution using five superimposed FGF structures as the search model. The structure shows that two novel disulfide bonds found in FGF19, one of which appears to be conserved among several of the other FGFs, stabilize extended loops. The key heparin-binding loops of FGF19 have radically different conformations and charge patterns, compared to other FGFs, correlating with the unusually low affinity of FGF19 for heparin. A model for the complex of FGF19 with FGFR4 demonstrates that unique sequences in both FGF19 and FGFR4 are key to the formation of the complex. The structure therefore offers a clear explanation for the unusual affinity of FGF19 for FGFR4 alone.
The crystal structure of fibroblast growth factor (FGF) 19 reveals novel features of the FGF family and offers a structural basis for its unusual receptor affinity.,Harmer NJ, Pellegrini L, Chirgadze D, Fernandez-Recio J, Blundell TL Biochemistry. 2004 Jan 27;43(3):629-40. PMID:14730967[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Holt JA, Luo G, Billin AN, Bisi J, McNeill YY, Kozarsky KF, Donahee M, Wang DY, Mansfield TA, Kliewer SA, Goodwin B, Jones SA. Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev. 2003 Jul 1;17(13):1581-91. Epub 2003 Jun 18. PMID:12815072 doi:10.1101/gad.1083503
- ↑ Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006 Jun 9;281(23):15694-700. Epub 2006 Apr 4. PMID:16597617 doi:10.1074/jbc.M601252200
- ↑ Kurosu H, Choi M, Ogawa Y, Dickson AS, Goetz R, Eliseenkova AV, Mohammadi M, Rosenblatt KP, Kliewer SA, Kuro-o M. Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem. 2007 Sep 14;282(37):26687-95. Epub 2007 Jul 10. PMID:17623664 doi:10.1074/jbc.M704165200
- ↑ Song KH, Li T, Owsley E, Strom S, Chiang JY. Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression. Hepatology. 2009 Jan;49(1):297-305. doi: 10.1002/hep.22627. PMID:19085950 doi:http://dx.doi.org/10.1002/hep.22627
- ↑ Harmer NJ, Pellegrini L, Chirgadze D, Fernandez-Recio J, Blundell TL. The crystal structure of fibroblast growth factor (FGF) 19 reveals novel features of the FGF family and offers a structural basis for its unusual receptor affinity. Biochemistry. 2004 Jan 27;43(3):629-40. PMID:14730967 doi:10.1021/bi035320k
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