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| | ==Crystal Structure Analysis of FGF1-Disaccharide(NI24) complex== | | ==Crystal Structure Analysis of FGF1-Disaccharide(NI24) complex== |
| - | <StructureSection load='3uda' size='340' side='right' caption='[[3uda]], [[Resolution|resolution]] 2.51Å' scene=''> | + | <StructureSection load='3uda' size='340' side='right'caption='[[3uda]], [[Resolution|resolution]] 2.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3uda]] is a 3 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=3UDA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UDA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3uda]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UDA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UDA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IDY:METHYL+2-O-SULFO-ALPHA-L-IDOPYRANOSIDURONIC+ACID'>IDY</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SUS:2-DEOXY-3,6-DI-O-SULFO-2-(SULFOAMINO)-ALPHA-D-GLUCOPYRANOSE'>SUS</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=IDY:METHYL+2-O-SULFO-ALPHA-L-IDOPYRANOSIDURONIC+ACID'>IDY</scene>, <scene name='pdbligand=SUS:2-DEOXY-3,6-DI-O-SULFO-2-(SULFOAMINO)-ALPHA-D-GLUCOPYRANOSE'>SUS</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ud7|3ud7]], [[3ud8|3ud8]], [[3ud9|3ud9]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ud7|3ud7]], [[3ud8|3ud8]], [[3ud9|3ud9]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FGF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FGF1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3uda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uda OCA], [http://pdbe.org/3uda PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3uda RCSB], [http://www.ebi.ac.uk/pdbsum/3uda PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3uda 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=3uda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uda OCA], [https://pdbe.org/3uda PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uda RCSB], [https://www.ebi.ac.uk/pdbsum/3uda PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uda ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FGF1_HUMAN FGF1_HUMAN]] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:8663044</ref> <ref>PMID:16597617</ref> <ref>PMID:20145243</ref> | + | [[https://www.uniprot.org/uniprot/FGF1_HUMAN FGF1_HUMAN]] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:8663044</ref> <ref>PMID:16597617</ref> <ref>PMID:20145243</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Fibroblast growth factor|Fibroblast growth factor]] | + | *[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Hung, S C]] | | [[Category: Hung, S C]] |
| | [[Category: Shi, Z]] | | [[Category: Shi, Z]] |
| | [[Category: Heparin/heparan sulfate binding]] | | [[Category: Heparin/heparan sulfate binding]] |
| | [[Category: Hormone]] | | [[Category: Hormone]] |
| Structural highlights
Function
[FGF1_HUMAN] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.[1] [2] [3]
Publication Abstract from PubMed
Several biological processes involve glycans, yet understanding their ligand specificities is impeded by their inherent diversity and difficult acquisition. Generating broad synthetic sugar libraries for bioevaluations is a powerful tool in unraveling glycan structural information. In the case of the widely distributed heparan sulfate (HS), however, the 48 theoretical possibilities for its repeating disaccharide call for synthetic approaches that should minimize the effort in an undoubtedly huge undertaking. Here we employed a divergent strategy to afford all 48 HS-based disaccharides from just two orthogonally protected disaccharide precursors. Different combinations and sequence of transformation steps were applied with many downstream intermediates leading up to multiple target products. With the full disaccharide library in hand, affinity screening with fibroblast growth factor-1 (FGF-1) revealed that four of the synthetic sugars bind to FGF-1. The molecular details of the interaction were further clarified through X-ray analysis of the sugar-protein cocrystals. The capability of comprehensive sugar libraries in providing key insights in glycan-ligand interaction is, thus, highlighted.
Divergent synthesis of 48 heparan sulfate-based disaccharides and probing the specific sugar-fibroblast growth factor-1 interaction.,Hu YP, Zhong YQ, Chen ZG, Chen CY, Shi Z, Zulueta MM, Ku CC, Lee PY, Wang CC, Hung SC J Am Chem Soc. 2012 Dec 26;134(51):20722-7. doi: 10.1021/ja3090065. Epub 2012 Dec, 14. PMID:23240683[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M. Receptor specificity of the fibroblast growth factor family. J Biol Chem. 1996 Jun 21;271(25):15292-7. PMID:8663044
- ↑ 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
- ↑ Fernandez IS, Cuevas P, Angulo J, Lopez-Navajas P, Canales-Mayordomo A, Gonzalez-Corrochano R, Lozano RM, Valverde S, Jimenez-Barbero J, Romero A, Gimenez-Gallego G. Gentisic acid, a compound associated with plant defense and a metabolite of aspirin, heads a new class of in vivo fibroblast growth factor inhibitors. J Biol Chem. 2010 Apr 9;285(15):11714-29. Epub 2010 Feb 9. PMID:20145243 doi:10.1074/jbc.M109.064618
- ↑ Hu YP, Zhong YQ, Chen ZG, Chen CY, Shi Z, Zulueta MM, Ku CC, Lee PY, Wang CC, Hung SC. Divergent synthesis of 48 heparan sulfate-based disaccharides and probing the specific sugar-fibroblast growth factor-1 interaction. J Am Chem Soc. 2012 Dec 26;134(51):20722-7. doi: 10.1021/ja3090065. Epub 2012 Dec, 14. PMID:23240683 doi:http://dx.doi.org/10.1021/ja3090065
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