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| - | [[Image:1q04.gif|left|200px]]<br /> | |
| - | <applet load="1q04" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1q04, resolution 1.80Å" /> | |
| - | '''Crystal structure of FGF-1, S50E/V51N'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Crystal structure of FGF-1, S50E/V51N== |
| - | The beta-turn is the most common type of nonrepetitive structure in, globular proteins, comprising ~25% of all residues; however, a detailed, understanding of effects of specific residues upon beta-turn stability and, conformation is lacking. Human acidic fibroblast growth factor (FGF-1) is, a member of the beta-trefoil superfold and contains a total of five, beta-hairpin structures (antiparallel beta-sheets connected by a reverse, turn). beta-Turns related by the characteristic threefold structural, symmetry of this superfold exhibit different primary structures, and in, some cases, different secondary structures. As such, they represent a, useful system with which to study the role that turn sequences play in, determining structure, stability, and folding of the protein. Two turns, related by the threefold structural symmetry, the beta4/beta5 and, beta8/beta9 turns, were subjected to both sequence-swapping and, poly-glycine substitution mutations, and the effects upon stability, folding, and structure were investigated. In the wild-type protein these, turns are of identical length, but exhibit different conformations. These, conformations were observed to be retained during sequence-swapping and, glycine substitution mutagenesis. The results indicate that the beta-turn, structure at these positions is not determined by the turn sequence., Structural analysis suggests that residues flanking the turn are a primary, structural determinant of the conformation within the turn. | + | <StructureSection load='1q04' size='340' side='right'caption='[[1q04]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1q04]] 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=1Q04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q04 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]] 1.8Å</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=1q04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q04 OCA], [https://pdbe.org/1q04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q04 RCSB], [https://www.ebi.ac.uk/pdbsum/1q04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q04 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/q0/1q04_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=1q04 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The beta-turn is the most common type of nonrepetitive structure in globular proteins, comprising ~25% of all residues; however, a detailed understanding of effects of specific residues upon beta-turn stability and conformation is lacking. Human acidic fibroblast growth factor (FGF-1) is a member of the beta-trefoil superfold and contains a total of five beta-hairpin structures (antiparallel beta-sheets connected by a reverse turn). beta-Turns related by the characteristic threefold structural symmetry of this superfold exhibit different primary structures, and in some cases, different secondary structures. As such, they represent a useful system with which to study the role that turn sequences play in determining structure, stability, and folding of the protein. Two turns related by the threefold structural symmetry, the beta4/beta5 and beta8/beta9 turns, were subjected to both sequence-swapping and poly-glycine substitution mutations, and the effects upon stability, folding, and structure were investigated. In the wild-type protein these turns are of identical length, but exhibit different conformations. These conformations were observed to be retained during sequence-swapping and glycine substitution mutagenesis. The results indicate that the beta-turn structure at these positions is not determined by the turn sequence. Structural analysis suggests that residues flanking the turn are a primary structural determinant of the conformation within the turn. |
| | | | |
| - | ==Disease==
| + | Sequence swapping does not result in conformation swapping for the beta4/beta5 and beta8/beta9 beta-hairpin turns in human acidic fibroblast growth factor.,Kim J, Lee J, Brych SR, Logan TM, Blaber M Protein Sci. 2005 Feb;14(2):351-9. Epub 2005 Jan 4. PMID:15632285<ref>PMID:15632285</ref> |
| - | 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]]
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1Q04 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 FMT as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Q04 OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1q04" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | Sequence swapping does not result in conformation swapping for the beta4/beta5 and beta8/beta9 beta-hairpin turns in human acidic fibroblast growth factor., Kim J, Lee J, Brych SR, Logan TM, Blaber M, Protein Sci. 2005 Feb;14(2):351-9. Epub 2005 Jan 4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15632285 15632285]
| + | *[[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: Kim, J.]] | + | [[Category: Kim J]] |
| - | [[Category: FMT]]
| + | |
| - | [[Category: beta-trefoil]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:49:10 2007''
| + | |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The beta-turn is the most common type of nonrepetitive structure in globular proteins, comprising ~25% of all residues; however, a detailed understanding of effects of specific residues upon beta-turn stability and conformation is lacking. Human acidic fibroblast growth factor (FGF-1) is a member of the beta-trefoil superfold and contains a total of five beta-hairpin structures (antiparallel beta-sheets connected by a reverse turn). beta-Turns related by the characteristic threefold structural symmetry of this superfold exhibit different primary structures, and in some cases, different secondary structures. As such, they represent a useful system with which to study the role that turn sequences play in determining structure, stability, and folding of the protein. Two turns related by the threefold structural symmetry, the beta4/beta5 and beta8/beta9 turns, were subjected to both sequence-swapping and poly-glycine substitution mutations, and the effects upon stability, folding, and structure were investigated. In the wild-type protein these turns are of identical length, but exhibit different conformations. These conformations were observed to be retained during sequence-swapping and glycine substitution mutagenesis. The results indicate that the beta-turn structure at these positions is not determined by the turn sequence. Structural analysis suggests that residues flanking the turn are a primary structural determinant of the conformation within the turn.
Sequence swapping does not result in conformation swapping for the beta4/beta5 and beta8/beta9 beta-hairpin turns in human acidic fibroblast growth factor.,Kim J, Lee J, Brych SR, Logan TM, Blaber M Protein Sci. 2005 Feb;14(2):351-9. Epub 2005 Jan 4. PMID:15632285[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
- ↑ Kim J, Lee J, Brych SR, Logan TM, Blaber M. Sequence swapping does not result in conformation swapping for the beta4/beta5 and beta8/beta9 beta-hairpin turns in human acidic fibroblast growth factor. Protein Sci. 2005 Feb;14(2):351-9. Epub 2005 Jan 4. PMID:15632285 doi:http://dx.doi.org/10.1110/ps.041094205
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