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2ntd
From Proteopedia
(New page: 200px<br /> <applet load="2ntd" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ntd, resolution 2.52Å" /> '''Human fibroblast gr...) |
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| - | [[Image:2ntd. | + | [[Image:2ntd.jpg|left|200px]]<br /><applet load="2ntd" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2ntd" size=" | + | |
caption="2ntd, resolution 2.52Å" /> | caption="2ntd, resolution 2.52Å" /> | ||
'''Human fibroblast growth factor-1 (140 amino acid form) with Cys117Val/Pro134Cys mutations'''<br /> | '''Human fibroblast growth factor-1 (140 amino acid form) with Cys117Val/Pro134Cys mutations'''<br /> | ||
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==Overview== | ==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. | 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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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602115 602115]], LADD syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602115 602115]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2NTD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FMT as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2NTD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FMT:'>FMT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NTD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: beta-trefoil]] | [[Category: beta-trefoil]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:25:07 2008'' |
Revision as of 12:25, 23 January 2008
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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 Homo sapiens with as ligand. 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
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