2hwm
From Proteopedia
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|PDB= 2hwm |SIZE=350|CAPTION= <scene name='initialview01'>2hwm</scene>, resolution 1.60Å | |PDB= 2hwm |SIZE=350|CAPTION= <scene name='initialview01'>2hwm</scene>, resolution 1.60Å | ||
|SITE= <scene name='pdbsite=AC1:Fmt+Binding+Site+For+Residue+B+141'>AC1</scene>, <scene name='pdbsite=AC2:Fmt+Binding+Site+For+Residue+A+141'>AC2</scene>, <scene name='pdbsite=AC3:Fmt+Binding+Site+For+Residue+A+142'>AC3</scene> and <scene name='pdbsite=AC4:Fmt+Binding+Site+For+Residue+B+142'>AC4</scene> | |SITE= <scene name='pdbsite=AC1:Fmt+Binding+Site+For+Residue+B+141'>AC1</scene>, <scene name='pdbsite=AC2:Fmt+Binding+Site+For+Residue+A+141'>AC2</scene>, <scene name='pdbsite=AC3:Fmt+Binding+Site+For+Residue+A+142'>AC3</scene> and <scene name='pdbsite=AC4:Fmt+Binding+Site+For+Residue+B+142'>AC4</scene> | ||
| - | |LIGAND= <scene name='pdbligand=FMT:FORMIC ACID'>FMT</scene> | + | |LIGAND= <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= FGF1, FGFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= FGF1, FGFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1jqz|1JQZ]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hwm OCA], [http://www.ebi.ac.uk/pdbsum/2hwm PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hwm RCSB]</span> | ||
}} | }} | ||
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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. | ||
| - | |||
| - | ==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== | ||
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[[Category: Lee, J.]] | [[Category: Lee, J.]] | ||
[[Category: Somasundaram, T.]] | [[Category: Somasundaram, T.]] | ||
| - | [[Category: FMT]] | ||
[[Category: beta-trefoil]] | [[Category: beta-trefoil]] | ||
[[Category: hormone/growth factor complex]] | [[Category: hormone/growth factor complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:36:30 2008'' |
Revision as of 00:36, 31 March 2008
| |||||||
| , resolution 1.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , and | ||||||
| Ligands: | |||||||
| Gene: | FGF1, FGFA (Homo sapiens) | ||||||
| Related: | 1JQZ
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of Lys12Val/Cys117Val mutant of human acidic fibroblast growth factor at 1.60 angstrom resolution
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
2HWM 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 Mon Mar 31 03:36:30 2008
