Copper metallochaperone

Copper metallochaperones are a specialized family of intracellular proteins dedicated to the safe transport and delivery of copper ions to specific target enzymes and organelles. Since free copper is highly redox-active and can catalyze the formation of damaging reactive oxygen species, these chaperones ensure that copper is sequestered and directed only to where it is needed (PMID: 10449070). Key members include Antioxidant 1 copper chaperone (ATOX1), which delivers copper to the secretory pathway via ATP7A and ATP7B; Copper chaperone for superoxide dismutase (CCS), which activates SOD1; and Cytochrome c oxidase copper chaperone (COX17), which shuttles copper to the mitochondria (PMID: 12142461). In clinical contexts, these proteins are significant because their dysregulation is linked to copper-overload disorders like Wilson's disease and copper-deficiency states like Menkes disease. Furthermore, copper metallochaperones, particularly ATOX1, are frequently overexpressed in various cancers to support accelerated proliferation and angiogenesis (PMID: 25533240). This overexpression makes them attractive therapeutic targets, leading to the development of small-molecule inhibitors like DCAC50 and chelators like tetrathiomolybdate (PMID: 26051517). These agents aim to disrupt copper trafficking to essential cuproenzymes, thereby inhibiting tumor growth and metastasis. Therapeutic challenges include maintaining systemic copper balance to avoid side effects like anemia and neutropenia.

Other names

Copper chaperoneCu-chaperoneIntracellular copper transport proteinCopper-binding protein

Inhibition of copper trafficking by binding to the chaperone's copper-binding site or sequestering copper ions to prevent their transfer to target enzymes and transporters (PMID: 25533240, PMID: 26051517).