2LQB
Metal binding repeat 2 of the Wilson disease protein (ATP7B)
Summary for 2LQB
| Entry DOI | 10.2210/pdb2lqb/pdb |
| NMR Information | BMRB: 18301 |
| Descriptor | Copper-transporting ATPase 2 (1 entity in total) |
| Functional Keywords | copper binding, hydrolase |
| Biological source | Homo sapiens (human) |
| Cellular location | Golgi apparatus, trans-Golgi network membrane; Multi-pass membrane protein (By similarity). Isoform 2: Cytoplasm. WND/140 kDa: Mitochondrion: P35670 |
| Total number of polymer chains | 1 |
| Total formula weight | 8427.71 |
| Authors | Nokhrin, S.,Dolgova, N.V.,Yu, C.,Dmitriev, O.Y. (deposition date: 2012-02-28, release date: 2013-07-03, Last modification date: 2024-05-15) |
| Primary citation | Dolgova, N.V.,Nokhrin, S.,Yu, C.H.,George, G.N.,Dmitriev, O.Y. Copper chaperone Atox1 interacts with the metal-binding domain of Wilson's disease protein in cisplatin detoxification. Biochem.J., 454:147-156, 2013 Cited by PubMed Abstract: Human copper transporters ATP7B (Wilson's disease protein) and ATP7A (Menkes' disease protein) have been implicated in tumour resistance to cisplatin, a widely used anticancer drug. Cisplatin binds to the copper-binding sites in the N-terminal domain of ATP7B, and this binding may be an essential step of cisplatin detoxification involving copper ATPases. In the present study, we demonstrate that cisplatin and a related platinum drug carboplatin produce the same adduct following reaction with MBD2 [metal-binding domain (repeat) 2], where platinum is bound to the side chains of the cysteine residues in the CxxC copper-binding motif. This suggests the same mechanism for detoxification of both drugs by ATP7B. Platinum can also be transferred to MBD2 from copper chaperone Atox1, which was shown previously to bind cisplatin. Binding of the free cisplatin and reaction with the cisplatin-loaded Atox1 produce the same protein-bound platinum intermediate. Transfer of platinum along the copper-transport pathways in the cell may serve as a mechanism of drug delivery to its target in the cell nucleus, and explain tumour-cell resistance to cisplatin associated with the overexpression of copper transporters ATP7B and ATP7A. PubMed: 23751120DOI: 10.1042/BJ20121656 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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