2hz9
Crystal structure of Lys12Val/Asn95Val/Cys117Val mutant of human acidic fibroblast growth factor at 1.70 angstrom resolution.
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OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[602115], LADD syndrome OMIM:[602115]
About this StructureAbout this Structure
2HZ9 is a Single protein structure of sequence from Homo sapiens with SO4 and FMT as ligands. Full crystallographic information is available from OCA.
ReferenceReference
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
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