View source for 2ntd

[[Image:2ntd.jpg|left|200px]]

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{{STRUCTURE_2ntd|  PDB=2ntd  |  SCENE=  }} 

'''Human fibroblast growth factor-1 (140 amino acid form) with Cys117Val/Pro134Cys mutations'''


==Overview==
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.

==About this Structure==
2NTD is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NTD OCA]. 

==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/17570396 17570396]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Blaber, M.]]
[[Category: Dubey, V K.]]
[[Category: Beta-trefoil]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 09:53:21 2008''