Difference between revisions of "Part:BBa K4134001"
Liu Jiankai (Talk | contribs) (→Description) |
Liu Jiankai (Talk | contribs) (→New discovery on silver binding site) |
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== Former information of Atox1 == | == Former information of Atox1 == | ||
| + | [[Image:Atox1-Cu-ions.gif|400px|thumb|right|Figure 1. Solution structures of (a) the Cu(I)Atox1 complex (PDB entry 1TL4) and (b) silver-substituted yeast metallothionein (PDB entry 1AOO). Images were made with VMD.]] | ||
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The chaperone Atox1 (initially called HAH1 for human Atx1 homologue) is a 68-amino-acid human protein essential for Cu homeostasis. The structures of apo- and Cu(I)-Atox1 have been resolved with X-ray diffraction (XRD) and NMR methods. The MxCxxC loop is a common feature of Cu-chaperones (like Atox1 in human, Atx1 in yeast, or CopZ in bacterium) and Cu-transporting P-type ATPases (such as ATP7A and ATP7B) and binds Cu(I) with two Cys residues in digonal coordination (Figure 1a). This motif is thought to play a key role in metal transfer between the two families of proteins. Nonphysiological metals like Cd(II) and Hg(II) can form stable complexes with Atox1 by binding to the two Cys of the MxCxxC motif; the formation of Ag(I)Atox1 complexes has been proven with spectroscopic methods, while the structure of the Ag(I) binding site had not been resolved till this year (2022). | The chaperone Atox1 (initially called HAH1 for human Atx1 homologue) is a 68-amino-acid human protein essential for Cu homeostasis. The structures of apo- and Cu(I)-Atox1 have been resolved with X-ray diffraction (XRD) and NMR methods. The MxCxxC loop is a common feature of Cu-chaperones (like Atox1 in human, Atx1 in yeast, or CopZ in bacterium) and Cu-transporting P-type ATPases (such as ATP7A and ATP7B) and binds Cu(I) with two Cys residues in digonal coordination (Figure 1a). This motif is thought to play a key role in metal transfer between the two families of proteins. Nonphysiological metals like Cd(II) and Hg(II) can form stable complexes with Atox1 by binding to the two Cys of the MxCxxC motif; the formation of Ag(I)Atox1 complexes has been proven with spectroscopic methods, while the structure of the Ag(I) binding site had not been resolved till this year (2022). | ||
</p> | </p> | ||
| + | Reference: Veronesi, Giulia, et al. "XAS investigation of silver (I) coordination in copper (I) biological binding sites." Inorganic Chemistry 54.24 (2015): 11688-11696. | ||
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== New discovery on silver binding site== | == New discovery on silver binding site== | ||
[[Image:Atox1-silver-cluster.gif|400px|thumb|right|Fig.2 Close-up view showing details of the tetrasilver cluster in Atox1 dimer.]] | [[Image:Atox1-silver-cluster.gif|400px|thumb|right|Fig.2 Close-up view showing details of the tetrasilver cluster in Atox1 dimer.]] | ||
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Atox1 binds the Ag+ and forms the tetrasilver clusters in Atox1 dimer. The details of the tetrasilver cluster in Atox1 dimer are shown in Fig. 2. In addition, the S–Ag–S bond angles of 168° are also consistent with the average values in linear and two coordinate Ag–S complexes that are found in the small molecule Cambridge Structural Database.38 Notably, the four silver ions have four Ag–Ag linkages with 3.17 ˚A and 2.83 ˚ A. The average dihedral angle of the four Ag–Ag linkages is 154˚. | Atox1 binds the Ag+ and forms the tetrasilver clusters in Atox1 dimer. The details of the tetrasilver cluster in Atox1 dimer are shown in Fig. 2. In addition, the S–Ag–S bond angles of 168° are also consistent with the average values in linear and two coordinate Ag–S complexes that are found in the small molecule Cambridge Structural Database.38 Notably, the four silver ions have four Ag–Ag linkages with 3.17 ˚A and 2.83 ˚ A. The average dihedral angle of the four Ag–Ag linkages is 154˚. | ||
</p> | </p> | ||
| − | + | Reference:Wang, Xiuxiu, et al. "An unexpected all-metal aromatic tetranuclear silver cluster in human copper chaperone Atox1." Chemical science 13.24 (2022): 7269-7275. | |
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Latest revision as of 16:20, 11 October 2022
Atox1
Description
Homo sapiens antioxidant 1 copper chaperone (ATOX1), mRNA. This gene can be expressed in prokaryotic systems.
As an Atx1-like copper chaperone, Atox1 is mainly responsible for delivering intracellular Cu(I) in eukaryotic cells, with very little perturbation by the Ag binding. Interestingly, Atox1 has been reported to combine silver ions in form of a tetrasilver cluster in its dimer.
Atox1 captures silver ions and paves the way for a new approach to synthesizing silver nanoparticles. And in our project, Atox1 fonctions as a silver-binding protein to replace AgBP2.
Former information of Atox1
The chaperone Atox1 (initially called HAH1 for human Atx1 homologue) is a 68-amino-acid human protein essential for Cu homeostasis. The structures of apo- and Cu(I)-Atox1 have been resolved with X-ray diffraction (XRD) and NMR methods. The MxCxxC loop is a common feature of Cu-chaperones (like Atox1 in human, Atx1 in yeast, or CopZ in bacterium) and Cu-transporting P-type ATPases (such as ATP7A and ATP7B) and binds Cu(I) with two Cys residues in digonal coordination (Figure 1a). This motif is thought to play a key role in metal transfer between the two families of proteins. Nonphysiological metals like Cd(II) and Hg(II) can form stable complexes with Atox1 by binding to the two Cys of the MxCxxC motif; the formation of Ag(I)Atox1 complexes has been proven with spectroscopic methods, while the structure of the Ag(I) binding site had not been resolved till this year (2022).
Reference: Veronesi, Giulia, et al. "XAS investigation of silver (I) coordination in copper (I) biological binding sites." Inorganic Chemistry 54.24 (2015): 11688-11696.
New discovery on silver binding site
Atox1 binds the Ag+ and forms the tetrasilver clusters in Atox1 dimer. The details of the tetrasilver cluster in Atox1 dimer are shown in Fig. 2. In addition, the S–Ag–S bond angles of 168° are also consistent with the average values in linear and two coordinate Ag–S complexes that are found in the small molecule Cambridge Structural Database.38 Notably, the four silver ions have four Ag–Ag linkages with 3.17 ˚A and 2.83 ˚ A. The average dihedral angle of the four Ag–Ag linkages is 154˚.
Reference:Wang, Xiuxiu, et al. "An unexpected all-metal aromatic tetranuclear silver cluster in human copper chaperone Atox1." Chemical science 13.24 (2022): 7269-7275.
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]