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[[Image:2erm.jpg|left|200px]]<br /><applet load="2erm" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2erm" />
'''Solution structure of a biologically active human FGF-1 monomer, complexed to a hexasaccharide heparin-analogue'''<br />


==Overview==
==Solution structure of a biologically active human FGF-1 monomer, complexed to a hexasaccharide heparin-analogue==
The 3D structure of a complex formed by the acidic fibroblast growth, factor (FGF-1) and a specifically designed synthetic heparin, hexasaccharide has been determined by NMR spectroscopy. This, hexasaccharide can substitute natural heparins in FGF-1 mitogenesis, assays, in spite of not inducing any apparent dimerization of the growth, factor. The use of this well defined synthetic heparin analogue has, allowed us to perform a detailed NMR structural analysis of the, heparin-FGF interaction, overcoming the limitations of NMR to deal with, the high molecular mass and heterogeneity of the FGF-1 oligomers formed in, the presence of natural heparin fragments. Our results confirm that, glycosaminoglycans induced FGF-1 dimerization either in a cis or trans, disposition with respect to the heparin chain is not an absolute, requirement for biological activity.
<StructureSection load='2erm' size='340' side='right'caption='[[2erm]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2erm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ERM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ERM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNS:N-SULFO-ALPHA-D-GLUCOSAMINE'>GNS</scene>, <scene name='pdbligand=IDR:L-IDURONIC+ACID'>IDR</scene>, <scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=NGY:2-(ACETYLAMINO)-2-DEOXY-6-O-SULFO-ALPHA-D-GLUCOPYRANOSE'>NGY</scene></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=2erm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2erm OCA], [https://pdbe.org/2erm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2erm RCSB], [https://www.ebi.ac.uk/pdbsum/2erm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2erm ProSAT]</span></td></tr>
</table>
== Function ==
[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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/er/2erm_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2erm ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602115 602115]], LADD syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602115 602115]]
*[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]]
 
== References ==
==About this Structure==
<references/>
2ERM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=IPA:'>IPA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ERM OCA].
__TOC__
 
</StructureSection>
==Reference==
Solution NMR structure of a human FGF-1 monomer, activated by a hexasaccharide heparin-analogue., Canales A, Lozano R, Lopez-Mendez B, Angulo J, Ojeda R, Nieto PM, Martin-Lomas M, Gimenez-Gallego G, Jimenez-Barbero J, FEBS J. 2006 Oct;273(20):4716-27. Epub 2006 Sep 21. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16995857 16995857]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Canales, A.]]
[[Category: Canales A]]
[[Category: Gimenez-Gallego, G.]]
[[Category: Gimenez-Gallego G]]
[[Category: Jimenez-Barbero, J.]]
[[Category: Jimenez-Barbero J]]
[[Category: Lozano, R.]]
[[Category: Lozano R]]
[[Category: Martin-Lomas, M.]]
[[Category: Martin-Lomas M]]
[[Category: Nieto, P.M.]]
[[Category: Nieto PM]]
[[Category: IPA]]
[[Category: fibroblast growth factor]]
[[Category: heparin-like hexasaccharide]]
[[Category: protein-carbohydrate complex]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:23:46 2008''

Latest revision as of 09:39, 1 May 2024

Solution structure of a biologically active human FGF-1 monomer, complexed to a hexasaccharide heparin-analogueSolution structure of a biologically active human FGF-1 monomer, complexed to a hexasaccharide heparin-analogue

Structural highlights

2erm is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
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