2hz9: Difference between revisions

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[[Image:2hz9.jpg|left|200px]]


{{Structure
==Crystal structure of Lys12Val/Asn95Val/Cys117Val mutant of human acidic fibroblast growth factor at 1.70 angstrom resolution.==
|PDB= 2hz9 |SIZE=350|CAPTION= <scene name='initialview01'>2hz9</scene>, resolution 1.70&Aring;
<StructureSection load='2hz9' size='340' side='right'caption='[[2hz9]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Residue+A+141'>AC1</scene>, <scene name='pdbsite=AC2:Fmt+Binding+Site+For+Residue+B+141'>AC2</scene>, <scene name='pdbsite=AC3:Fmt+Binding+Site+For+Residue+A+142'>AC3</scene>, <scene name='pdbsite=AC4:Fmt+Binding+Site+For+Residue+B+142'>AC4</scene> and <scene name='pdbsite=AC5:Fmt+Binding+Site+For+Residue+B+143'>AC5</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
<table><tr><td colspan='2'>[[2hz9]] is a 2 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=2HZ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HZ9 FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
|GENE= FGF1, FGFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hz9 OCA], [https://pdbe.org/2hz9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hz9 RCSB], [https://www.ebi.ac.uk/pdbsum/2hz9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hz9 ProSAT]</span></td></tr>
|RELATEDENTRY=[[1jqz|1JQZ]]
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hz9 OCA], [http://www.ebi.ac.uk/pdbsum/2hz9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hz9 RCSB]</span>
== 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/hz/2hz9_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=2hz9 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.


'''Crystal structure of Lys12Val/Asn95Val/Cys117Val mutant of human acidic fibroblast growth factor at 1.70 angstrom resolution.'''
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>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2hz9" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]]
 
== References ==
==About this Structure==
<references/>
2HZ9 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=2HZ9 OCA].
__TOC__
 
</StructureSection>
==Reference==
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]
[[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: Lee, J.]]
[[Category: Lee J]]
[[Category: Somasundaram, T.]]
[[Category: Somasundaram T]]
[[Category: beta-trefoil]]
[[Category: hormone/growth factor complex]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:37:35 2008''
Retrieved from "https://proteopedia.org/2hz9"