6A72

Copper transporter protein

6A72 の概要

• エントリーDOI: 10.2210/pdb6a72/pdb
• 分子名称: ATP7B protein, dioxo(di-mu-sulfide)dimolybdenum, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: copper transporter protein, metal transport
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15142.94

構造登録者

Chen, W.B. (登録日: 2018-07-01, 公開日: 2019-04-03, 最終更新日: 2023-11-22)

主引用文献

Fang, T.,Chen, W.,Sheng, Y.,Yuan, S.,Tang, Q.,Li, G.,Huang, G.,Su, J.,Zhang, X.,Zang, J.,Liu, Y.
Tetrathiomolybdate induces dimerization of the metal-binding domain of ATPase and inhibits platination of the protein.
Nat Commun, 10:186-186, 2019

PubMed Abstract: Tetrathiomolybdate (TM) is used in the clinic for the treatment of Wilson's disease by targeting the cellular copper efflux protein ATP7B (WLN). Interestingly, both TM and WLN are associated with the efficacy of cisplatin, a widely used anticancer drug. Herein, we show that TM induces dimerization of the metal-binding domain of ATP7B (WLN4) through a unique sulfur-bridged MoSO cluster. TM expels copper ions from Cu-WLN4 and forms a copper-free dimer. The binding of Mo to cysteine residues of WLN4 inhibits platination of the protein. Reaction with multi-domain proteins indicates that TM can also connect two domains in the same molecule, forming Mo-bridged intramolecular crosslinks. These results provide structural and chemical insight into the mechanism of action of TM against ATPase, and reveal the molecular mechanism by which TM attenuates the cisplatin resistance mediated by copper efflux proteins.

PubMed: 30643139
DOI: 10.1038/s41467-018-08102-z

実験手法

X-RAY DIFFRACTION (2.1 Å)