2HWM
Crystal structure of Lys12Val/Cys117Val mutant of human acidic fibroblast growth factor at 1.60 angstrom resolution
Summary for 2HWM
Entry DOI | 10.2210/pdb2hwm/pdb |
Related | 1JQZ |
Descriptor | Heparin-binding growth factor 1, FORMIC ACID (3 entities in total) |
Functional Keywords | beta-trefoil, hormone-growth factor complex, hormone/growth factor |
Biological source | Homo sapiens (human) |
Cellular location | Secreted: P05230 |
Total number of polymer chains | 2 |
Total formula weight | 33489.47 |
Authors | Dubey, V.K.,Lee, J.,Somasundaram, T.,Blaber, M. (deposition date: 2006-08-01, release date: 2007-06-12, Last modification date: 2023-08-30) |
Primary citation | Dubey, V.K.,Lee, J.,Somasundaram, T.,Blaber, S.,Blaber, M. Spackling the crack: stabilizing human fibroblast growth factor-1 by targeting the N and C terminus beta-strand interactions. J.Mol.Biol., 371:256-268, 2007 Cited by PubMed Abstract: 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. PubMed: 17570396DOI: 10.1016/j.jmb.2007.05.065 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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