2hwm: Difference between revisions

Revision as of 06:48, 4 May 2008

Crystal structure of Lys12Val/Cys117Val mutant of human acidic fibroblast growth factor at 1.60 angstrom resolution

OverviewOverview

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 StructureAbout this Structure

2HWM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 May 4 06:48:11 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2hwm.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2hwm |SIZE=350|CAPTION= <scene name='initialview01'>2hwm</scene>, resolution 1.60&Aring;
+The line below this paragraph, containing "STRUCTURE_2hwm", creates the "Structure Box" on the page.
-|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>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE= FGF1, FGFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2hwm|  PDB=2hwm  |  SCENE=  }}
-|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>
-}}
 '''Crystal structure of Lys12Val/Cys117Val mutant of human acidic fibroblast growth factor at 1.60 angstrom resolution'''
@@ Line 29: / Line 26: @@
 [[Category: Lee, J.]]
 [[Category: Somasundaram, T.]]
-[[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 Sun May  4 06:48:11 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:36:30 2008''