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[[Image:2ntd.jpg|left|200px]]
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{{STRUCTURE_2ntd|  PDB=2ntd  |  SCENE=  }}
'''Human fibroblast growth factor-1 (140 amino acid form) with Cys117Val/Pro134Cys mutations'''


==Human fibroblast growth factor-1 (140 amino acid form) with Cys117Val/Pro134Cys mutations==
<StructureSection load='2ntd' size='340' side='right'caption='[[2ntd]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ntd]] is a 4 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=2NTD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NTD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.52&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=2ntd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ntd OCA], [https://pdbe.org/2ntd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ntd RCSB], [https://www.ebi.ac.uk/pdbsum/2ntd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ntd 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/nt/2ntd_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=2ntd ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The beta-trefoil protein human fibroblast growth factor-1 (FGF-1) is made up of a six-stranded antiparallel beta-barrel closed off on one end by three beta-hairpins, thus exhibiting a 3-fold axis of structural symmetry. The N and C terminus beta-strands hydrogen bond to each other and their interaction is postulated from both NMR and X-ray structure data to be important in folding and stability. Specific mutations within the adjacent N and C terminus beta-strands of FGF-1 are shown to provide a substantial increase in stability. This increase is largely correlated with an increased folding rate constant, and with a smaller but significant decrease in the unfolding rate constant. A series of stabilizing mutations are subsequently combined and result in a doubling of the DeltaG value of unfolding. When taken in the context of previous studies of stabilizing mutations, the results indicate that although FGF-1 is known for generally poor thermal stability, the beta-trefoil architecture appears capable of substantial thermal stability. Targeting stabilizing mutations within the N and C terminus beta-strand interactions of a beta-barrel architecture may be a generally useful approach to increase protein stability. Such stabilized mutations of FGF-1 are shown to exhibit significant increases in effective mitogenic potency, and may prove useful as "second generation" forms of FGF-1 for application in angiogenic therapy.


==Overview==
Spackling the crack: stabilizing human fibroblast growth factor-1 by targeting the N and C terminus beta-strand interactions.,Dubey VK, Lee J, Somasundaram T, Blaber S, Blaber M J Mol Biol. 2007 Aug 3;371(1):256-68. Epub 2007 May 31. PMID:17570396<ref>PMID:17570396</ref>
The beta-trefoil protein human fibroblast growth factor-1 (FGF-1) is made up of a six-stranded antiparallel beta-barrel closed off on one end by three beta-hairpins, thus exhibiting a 3-fold axis of structural symmetry. The N and C terminus beta-strands hydrogen bond to each other and their interaction is postulated from both NMR and X-ray structure data to be important in folding and stability. Specific mutations within the adjacent N and C terminus beta-strands of FGF-1 are shown to provide a substantial increase in stability. This increase is largely correlated with an increased folding rate constant, and with a smaller but significant decrease in the unfolding rate constant. A series of stabilizing mutations are subsequently combined and result in a doubling of the DeltaG value of unfolding. When taken in the context of previous studies of stabilizing mutations, the results indicate that although FGF-1 is known for generally poor thermal stability, the beta-trefoil architecture appears capable of substantial thermal stability. Targeting stabilizing mutations within the N and C terminus beta-strand interactions of a beta-barrel architecture may be a generally useful approach to increase protein stability. Such stabilized mutations of FGF-1 are shown to exhibit significant increases in effective mitogenic potency, and may prove useful as "second generation" forms of FGF-1 for application in angiogenic therapy.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2NTD 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=2NTD OCA].
</div>
<div class="pdbe-citations 2ntd" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Spackling the crack: stabilizing human fibroblast growth factor-1 by targeting the N and C terminus beta-strand interactions., Dubey VK, Lee J, Somasundaram T, Blaber S, Blaber M, J Mol Biol. 2007 Aug 3;371(1):256-68. Epub 2007 May 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17570396 17570396]
*[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Blaber, M.]]
[[Category: Blaber M]]
[[Category: Dubey, V K.]]
[[Category: Dubey VK]]
[[Category: Beta-trefoil]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 09:53:21 2008''
Retrieved from "https://proteopedia.org/2ntd"