1zd6
From Proteopedia
(New page: 200px<br /> <applet load="1zd6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zd6, resolution 1.90Å" /> '''Crystal structure o...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1zd6.gif|left|200px]]<br /> | + | [[Image:1zd6.gif|left|200px]]<br /><applet load="1zd6" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1zd6" size=" | + | |
caption="1zd6, resolution 1.90Å" /> | caption="1zd6, resolution 1.90Å" /> | ||
'''Crystal structure of human transthyretin with bound chloride'''<br /> | '''Crystal structure of human transthyretin with bound chloride'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Transthyretin amyloid formation occurs through a process of tetramer | + | Transthyretin amyloid formation occurs through a process of tetramer destabilization and partial unfolding. Small molecules, including the natural ligand thyroxine, stabilize the tetrameric form of the protein, and serve as inhibitors of amyloid formation. Crucial for TTR's ligand-binding properties are its three halogen-binding sites situated at the hormone-binding channel. In this study, we have performed a structural characterization of the binding of two halides, iodide and chloride, to TTR. Chlorides are known to shield charge repulsions at the tetrameric interface of TTR, which improve tetramer stability of the protein. Our study shows that iodides, like chlorides, provide tetramer stabilization in a concentration-dependent manner and at concentrations approximately 15-fold below that of chlorides. To elucidate binding sites of the halides, we took advantage of the anomalous scattering of iodide and used the single-wavelength anomalous dispersion (SAD) method to solve the iodide-bound TTR structure at 1.8 A resolution. The structure of chloride-bound TTR was determined at 1.9 A resolution using difference Fourier techniques. The refined structures showed iodides and chlorides bound at two of the three halogen-binding sites located at the hydrophobic channel. These sites therefore also function as halide-binding sites. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1ZD6 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 CL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1ZD6 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=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZD6 OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Hornberg, A.]] | [[Category: Hornberg, A.]] | ||
| - | [[Category: Hultdin, U | + | [[Category: Hultdin, U W.]] |
[[Category: Olofsson, A.]] | [[Category: Olofsson, A.]] | ||
| - | [[Category: Sauer-Eriksson, A | + | [[Category: Sauer-Eriksson, A E.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: transport]] | [[Category: transport]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:14:24 2008'' |
Revision as of 14:14, 21 February 2008
|
Crystal structure of human transthyretin with bound chloride
Contents |
Overview
Transthyretin amyloid formation occurs through a process of tetramer destabilization and partial unfolding. Small molecules, including the natural ligand thyroxine, stabilize the tetrameric form of the protein, and serve as inhibitors of amyloid formation. Crucial for TTR's ligand-binding properties are its three halogen-binding sites situated at the hormone-binding channel. In this study, we have performed a structural characterization of the binding of two halides, iodide and chloride, to TTR. Chlorides are known to shield charge repulsions at the tetrameric interface of TTR, which improve tetramer stability of the protein. Our study shows that iodides, like chlorides, provide tetramer stabilization in a concentration-dependent manner and at concentrations approximately 15-fold below that of chlorides. To elucidate binding sites of the halides, we took advantage of the anomalous scattering of iodide and used the single-wavelength anomalous dispersion (SAD) method to solve the iodide-bound TTR structure at 1.8 A resolution. The structure of chloride-bound TTR was determined at 1.9 A resolution using difference Fourier techniques. The refined structures showed iodides and chlorides bound at two of the three halogen-binding sites located at the hydrophobic channel. These sites therefore also function as halide-binding sites.
Disease
Known diseases associated with this structure: Amyloid neuropathy, familial, several allelic types OMIM:[176300], Amyloidosis, senile systemic OMIM:[176300], Carpal tunnel syndrome, familial OMIM:[176300], Dystransthyretinemic hyperthyroxinemia OMIM:[176300]
About this Structure
1ZD6 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
The effect of iodide and chloride on transthyretin structure and stability., Hornberg A, Hultdin UW, Olofsson A, Sauer-Eriksson AE, Biochemistry. 2005 Jul 5;44(26):9290-9. PMID:15981995
Page seeded by OCA on Thu Feb 21 16:14:24 2008
