2HZ9

Crystal structure of Lys12Val/Asn95Val/Cys117Val mutant of human acidic fibroblast growth factor at 1.70 angstrom resolution.

Summary for 2HZ9

• Entry DOI: 10.2210/pdb2hz9/pdb
• Related: 1JQZ
• Descriptor: Heparin-binding growth factor 1, SULFATE ION, FORMIC ACID, ... (4 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: 33555.59

Authors

Dubey, V.K.,Lee, J.,Somasundaram, T.,Blaber, M. (deposition date: 2006-08-08, release date: 2007-06-19, 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

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: 17570396
DOI: 10.1016/j.jmb.2007.05.065

Experimental method

X-RAY DIFFRACTION (1.7 Å)