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2hw9

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[[Image:2hw9.jpg|left|200px]]
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{{STRUCTURE_2hw9| PDB=2hw9 | SCENE= }}
{{STRUCTURE_2hw9| PDB=2hw9 | SCENE= }}
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'''Crystal structure of Lys12Cys/Cys117Val mutant of human acidic fibroblast Growth factor at 1.60 angstrom resolution.'''
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===Crystal structure of Lys12Cys/Cys117Val mutant of human acidic fibroblast Growth factor at 1.60 angstrom resolution.===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_17570396}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 17570396 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17570396}}
==About this Structure==
==About this Structure==
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[[Category: Beta-trefoil]]
[[Category: Beta-trefoil]]
[[Category: Hormone/growth factor complex]]
[[Category: Hormone/growth factor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:47:28 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 14:10:12 2008''

Revision as of 11:10, 27 July 2008

Template:STRUCTURE 2hw9

Crystal structure of Lys12Cys/Cys117Val mutant of human acidic fibroblast Growth factor at 1.60 angstrom resolution.

Template:ABSTRACT PUBMED 17570396

About this Structure

2HW9 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from 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:17570396

Page seeded by OCA on Sun Jul 27 14:10:12 2008

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