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| | ==Crystal structure of C16T/K12V/C117V/P134V mutant of human acidic fibroblast growth factor== | | ==Crystal structure of C16T/K12V/C117V/P134V mutant of human acidic fibroblast growth factor== |
| - | <StructureSection load='4q9p' size='340' side='right' caption='[[4q9p]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4q9p' size='340' side='right'caption='[[4q9p]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4q9p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q9P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q9P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4q9p]] 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=4Q9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q9P FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2afg|2afg]], [[1jqz|1jqz]], [[1rg8|1rg8]], [[4q91|4q91]], [[4q9g|4q9g]], [[4qal|4qal]], [[1jy0|1jy0]], [[3fjh|3fjh]], [[3fjf|3fjf]], [[3fje|3fje]], [[3fjk|3fjk]]</td></tr> | + | </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='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=4q9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q9p RCSB], [http://www.ebi.ac.uk/pdbsum/4q9p PDBsum]</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=4q9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9p OCA], [https://pdbe.org/4q9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q9p RCSB], [https://www.ebi.ac.uk/pdbsum/4q9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q9p 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;">
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| - | == Publication Abstract from PubMed ==
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| - | Buried free-cysteine (Cys) residues can contribute to an irreversible unfolding pathway that promotes protein aggregation, increases immunogenic potential, and significantly reduces protein functional half-life. Consequently, mutation of buried free-Cys residues can result in significant improvement in the storage, reconstitution, and pharmacokinetic properties of protein-based therapeutics. Mutational design to eliminate buried free-Cys residues typically follows one of two common heuristics: either substitution by Ser (polar and isosteric), or substitution by Ala or Val (hydrophobic); however, a detailed structural and thermodynamic understanding of Cys mutations is lacking. We report a comprehensive structure and stability study of Ala, Ser, Thr, and Val mutations at each of the three buried free-Cys positions (Cys16, Cys83, and Cys117) in fibroblast growth factor-1. Mutation was almost universally destabilizing, indicating a general optimization for the wild-type Cys, including van der Waals and H-bond interactions. Structural response to Cys mutation characteristically involved changes to maintain, or effectively substitute, local H-bond interactions-by either structural collapse to accommodate the smaller oxygen radius of Ser/Thr, or conversely, expansion to enable inclusion of novel H-bonding solvent. Despite the diverse structural effects, the least destabilizing average substitution at each position was Ala, and not isosteric Ser. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:566-576, 2015.
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| - | Mutation choice to eliminate buried free cysteines in protein therapeutics.,Xia X, Longo LM, Blaber M J Pharm Sci. 2015 Feb;104(2):566-76. doi: 10.1002/jps.24188. Epub 2014 Oct 13. PMID:25312595<ref>PMID:25312595</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | ==See Also== |
| - | </div>
| + | *[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Blaber, M]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Xia, X]] | + | [[Category: Large Structures]] |
| - | [[Category: Beta-trefoil]] | + | [[Category: Blaber M]] |
| - | [[Category: Extracellular matrix]] | + | [[Category: Xia X]] |
| - | [[Category: Fgfr binding]]
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| - | [[Category: Growth factor]]
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| - | [[Category: Heparin binding]]
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| - | [[Category: Protein binding]]
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| 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]
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
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