Intracellular copper-binding proteins and ligands

Intracellular copper-binding proteins and ligands constitute a complex network responsible for maintaining copper homeostasis and preventing the toxicity of free copper ions (Source: PubMed PMID 24553174). This system includes copper chaperones such as Antioxidant 1 copper chaperone (ATOX1), Copper chaperone for superoxide dismutase (CCS), and Cytochrome c oxidase copper chaperone (COX17), which traffic copper to specific organelles or enzymes (Source: UniProt P55957, O14618). Additionally, storage proteins like metallothioneins and small-molecule ligands like glutathione play critical roles in sequestering and buffering the intracellular copper pool (Source: PubMed PMID 21333510). Dysregulation of this network is central to genetic disorders such as Wilson disease and Menkes disease, and it plays a significant role in cancer progression by supporting angiogenesis and oncogenic signaling (Source: NIH StatPearls NBK441990). Pharmacological intervention typically involves copper chelators like trientine and D-penicillamine to remove excess metal or ionophores like elesclomol to redistribute copper for pro-oxidant effects in cancer cells (Source: PubMed PMID 29305512). These therapies aim to restore copper balance or exploit the metal's redox activity for therapeutic benefit.

Other names

Copper chaperonesMetallochaperonesIntracellular copper poolCopper-binding proteins

Drugs targeting this system act through several mechanisms: chelators like trientine and D-penicillamine bind and facilitate the excretion of copper; zinc salts induce the synthesis of endogenous metallothioneins to sequester copper in intestinal cells; and copper ionophores like elesclomol increase intracellular copper to levels that induce oxidative stress and cell death in cancer cells (Source: PubMed PMID 29305512, NIH StatPearls NBK441990).