2p39

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[[Image:2p39.gif|left|200px]]
 
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==Crystal structure of human FGF23==
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The line below this paragraph, containing "STRUCTURE_2p39", creates the "Structure Box" on the page.
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<StructureSection load='2p39' size='340' side='right'caption='[[2p39]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2p39]] 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=2P39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P39 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GU4:2,3,4,6-TETRA-O-SULFONATO-ALPHA-D-GLUCOPYRANOSE'>GU4</scene>, <scene name='pdbligand=PRD_900013:sucrose+octasulfate'>PRD_900013</scene>, <scene name='pdbligand=YYJ:1,3,4,6-tetra-O-sulfo-beta-D-fructofuranose'>YYJ</scene></td></tr>
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{{STRUCTURE_2p39| PDB=2p39 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2p39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p39 OCA], [https://pdbe.org/2p39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p39 RCSB], [https://www.ebi.ac.uk/pdbsum/2p39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p39 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/FGF23_HUMAN FGF23_HUMAN] Defects in FGF23 are the cause of autosomal dominant hypophosphataemic rickets (ADHR) [MIM:[https://omim.org/entry/193100 193100]. ADHR is characterized by low serum phosphorus concentrations, rickets, osteomalacia, leg deformities, short stature, bone pain and dental abscesses.<ref>PMID:11062477</ref> <ref>PMID:11409890</ref> <ref>PMID:16638743</ref> Defects in FGF23 are a cause of hyperphosphatemic familial tumoral calcinosis (HFTC) [MIM:[https://omim.org/entry/211900 211900]. HFTC is a severe autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues.<ref>PMID:15590700</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/FGF23_HUMAN FGF23_HUMAN] Regulator of phosphate homeostasis. Inhibits renal tubular phosphate transport by reducing SLC34A1 levels. Upregulates EGR1 expression in the presence of KL (By similarity). Acts directly on the parathyroid to decrease PTH secretion (By similarity). Regulator of vitamin-D metabolism. Negatively regulates osteoblast differentiation and matrix mineralization.<ref>PMID:11062477</ref> <ref>PMID:11409890</ref> <ref>PMID:15040831</ref> <ref>PMID:16597617</ref> <ref>PMID:18282132</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p3/2p39_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2p39 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Unique among fibroblast growth factors (FGFs), FGF19, -21, and -23 act in an endocrine fashion to regulate energy, bile acid, glucose, lipid, phosphate, and vitamin D homeostasis. These FGFs require the presence of Klotho/betaKlotho in their target tissues. Here, we present the crystal structures of FGF19 alone and FGF23 in complex with sucrose octasulfate, a disaccharide chemically related to heparin. The conformation of the heparin-binding region between beta strands 10 and 12 in FGF19 and FGF23 diverges completely from the common conformation adopted by paracrine-acting FGFs. A cleft between this region and the beta1-beta2 loop, the other heparin-binding region, precludes direct interaction between heparin/heparan sulfate and backbone atoms of FGF19/23. This reduces the heparin-binding affinity of these ligands and confers endocrine function. Klotho/betaKlotho have evolved as a compensatory mechanism for the poor ability of heparin/heparan sulfate to promote binding of FGF19, -21, and -23 to their cognate receptors.
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'''Crystal structure of human FGF23'''
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Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members.,Goetz R, Beenken A, Ibrahimi OA, Kalinina J, Olsen SK, Eliseenkova AV, Xu C, Neubert TA, Zhang F, Linhardt RJ, Yu X, White KE, Inagaki T, Kliewer SA, Yamamoto M, Kurosu H, Ogawa Y, Kuro-o M, Lanske B, Razzaque MS, Mohammadi M Mol Cell Biol. 2007 May;27(9):3417-28. Epub 2007 Mar 5. PMID:17339340<ref>PMID:17339340</ref>
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==Overview==
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Unique among fibroblast growth factors (FGFs), FGF19, -21, and -23 act in an endocrine fashion to regulate energy, bile acid, glucose, lipid, phosphate, and vitamin D homeostasis. These FGFs require the presence of Klotho/betaKlotho in their target tissues. Here, we present the crystal structures of FGF19 alone and FGF23 in complex with sucrose octasulfate, a disaccharide chemically related to heparin. The conformation of the heparin-binding region between beta strands 10 and 12 in FGF19 and FGF23 diverges completely from the common conformation adopted by paracrine-acting FGFs. A cleft between this region and the beta1-beta2 loop, the other heparin-binding region, precludes direct interaction between heparin/heparan sulfate and backbone atoms of FGF19/23. This reduces the heparin-binding affinity of these ligands and confers endocrine function. Klotho/betaKlotho have evolved as a compensatory mechanism for the poor ability of heparin/heparan sulfate to promote binding of FGF19, -21, and -23 to their cognate receptors.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2P39 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P39 OCA].
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</div>
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<div class="pdbe-citations 2p39" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members., Goetz R, Beenken A, Ibrahimi OA, Kalinina J, Olsen SK, Eliseenkova AV, Xu C, Neubert TA, Zhang F, Linhardt RJ, Yu X, White KE, Inagaki T, Kliewer SA, Yamamoto M, Kurosu H, Ogawa Y, Kuro-o M, Lanske B, Razzaque MS, Mohammadi M, Mol Cell Biol. 2007 May;27(9):3417-28. Epub 2007 Mar 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17339340 17339340]
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*[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Mohammadi, M.]]
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[[Category: Mohammadi M]]
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[[Category: Atypical beta-trefoil fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 12:15:07 2008''
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Current revision

Crystal structure of human FGF23

PDB ID 2p39

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