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http://purl.uniprot.org/citations/17570396 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
http://purl.uniprot.org/citations/17570396 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2007.05.065"xsd:string |
http://purl.uniprot.org/citations/17570396 | http://purl.uniprot.org/core/author | "Lee J."xsd:string |
http://purl.uniprot.org/citations/17570396 | http://purl.uniprot.org/core/author | "Somasundaram T."xsd:string |
http://purl.uniprot.org/citations/17570396 | http://purl.uniprot.org/core/author | "Blaber M."xsd:string |
http://purl.uniprot.org/citations/17570396 | http://purl.uniprot.org/core/author | "Dubey V.K."xsd:string |
http://purl.uniprot.org/citations/17570396 | http://purl.uniprot.org/core/author | "Blaber S."xsd:string |
http://purl.uniprot.org/citations/17570396 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
http://purl.uniprot.org/citations/17570396 | http://purl.uniprot.org/core/name | "J Mol Biol"xsd:string |
http://purl.uniprot.org/citations/17570396 | http://purl.uniprot.org/core/pages | "256-268"xsd:string |
http://purl.uniprot.org/citations/17570396 | http://purl.uniprot.org/core/title | "Spackling the crack: stabilizing human fibroblast growth factor-1 by targeting the N and C terminus beta-strand interactions."xsd:string |
http://purl.uniprot.org/citations/17570396 | http://purl.uniprot.org/core/volume | "371"xsd:string |
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