2p39
From Proteopedia
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|PDB= 2p39 |SIZE=350|CAPTION= <scene name='initialview01'>2p39</scene>, resolution 1.5Å | |PDB= 2p39 |SIZE=350|CAPTION= <scene name='initialview01'>2p39</scene>, resolution 1.5Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=SCR:SUCROSE OCTASULFATE'>SCR</scene> | + | |LIGAND= <scene name='pdbligand=SCR:SUCROSE+OCTASULFATE'>SCR</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= FGF23, HYPF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= FGF23, HYPF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2p23|2P23]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p39 OCA], [http://www.ebi.ac.uk/pdbsum/2p39 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2p39 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Hypophosphatemic rickets, autosomal dominant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605380 605380]], Osteomalacia, tumor-induced OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605380 605380]], Tumoral calcinosis, hyperphosphatemic, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605380 605380]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Mohammadi, M.]] | [[Category: Mohammadi, M.]] | ||
| - | [[Category: SCR]] | ||
[[Category: atypical beta-trefoil fold]] | [[Category: atypical beta-trefoil fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:28:16 2008'' |
Revision as of 01:28, 31 March 2008
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| , resolution 1.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | FGF23, HYPF (Homo sapiens) | ||||||
| Related: | 2P23
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human FGF23
Overview
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.
About this Structure
2P39 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Mar 31 04:28:16 2008
