3fj9: Difference between revisions

Latest revision as of 06:46, 6 September 2023

Crystal structure of F85W mutant of Human acidic fibroblast growth factor

Structural highlights

3fj9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:	FMT
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.

Publication Abstract from PubMed

Protein biopharmaceuticals are an important and growing area of human therapeutics; however, the intrinsic property of proteins to adopt alternative conformations (such as during protein unfolding and aggregation) presents numerous challenges, limiting their effective application as biopharmaceuticals. Using fibroblast growth factor-1 as model system, we describe a cooperative interaction between the intrinsic property of thermostability and the reactivity of buried free-cysteine residues that can substantially modulate protein functional half-life. A mutational strategy that combines elimination of buried free cysteines and secondary mutations that enhance thermostability to achieve a substantial gain in functional half-life is described. Furthermore, the implementation of this design strategy utilizing stabilizing mutations within the core region resulted in a mutant protein that is essentially indistinguishable from wild type as regard protein surface and solvent structure, thus minimizing the immunogenic potential of the mutations. This design strategy should be generally applicable to soluble globular proteins containing buried free-cysteine residues.

The interaction between thermodynamic stability and buried free cysteines in regulating the functional half-life of fibroblast growth factor-1.,Lee J, Blaber M J Mol Biol. 2009 Oct 16;393(1):113-27. Epub 2009 Aug 18. PMID:19695265^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Lee J, Blaber M. The interaction between thermodynamic stability and buried free cysteines in regulating the functional half-life of fibroblast growth factor-1. J Mol Biol. 2009 Oct 16;393(1):113-27. Epub 2009 Aug 18. PMID:19695265 doi:10.1016/j.jmb.2009.08.026

Proteopedia Page Contributors and Editors (what is this?)

OCA

[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

[4] Lee J, Blaber M. The interaction between thermodynamic stability and buried free cysteines in regulating the functional half-life of fibroblast growth factor-1. J Mol Biol. 2009 Oct 16;393(1):113-27. Epub 2009 Aug 18. PMID:19695265 doi:10.1016/j.jmb.2009.08.026

[1]

[2]

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[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='3fj9' size='340' side='right'caption='[[3fj9]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3fj9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FJ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FJ9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3fj9]] 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=3FJ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FJ9 FirstGlance]. <br>
-</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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1jqz|1jqz]], [[3fgm|3fgm]], [[3fj8|3fj8]], [[3fja|3fja]], [[3fjb|3fjb]], [[3fjc|3fjc]], [[3fjd|3fjd]], [[3fje|3fje]], [[3fjf|3fjf]], [[3fjh|3fjh]], [[3fji|3fji]], [[3fjj|3fjj]], [[3fjk|3fjk]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FGF1, FGFA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3fj9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fj9 OCA], [https://pdbe.org/3fj9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fj9 RCSB], [https://www.ebi.ac.uk/pdbsum/3fj9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fj9 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>
+[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]]
@@ Line 37: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Blaber, M]]
+[[Category: Blaber M]]
-[[Category: Lee, J]]
+[[Category: Lee J]]
-[[Category: Acetylation]]
-[[Category: Angiogenesis]]
-[[Category: Beta-trefoil]]
-[[Category: Developmental protein]]
-[[Category: Differentiation]]
-[[Category: Growth factor]]
-[[Category: Heparin-binding]]
-[[Category: Hormone]]
-[[Category: Mitogen]]
-[[Category: Polymorphism]]

3fj9: Difference between revisions

Latest revision as of 06:46, 6 September 2023

Crystal structure of F85W mutant of Human acidic fibroblast growth factor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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