Tetrathiomolybdate Inhibits Copper Trafficking Proteins Through Metal Cluster Formation

Abstract
Targeting Copper Clusters: Tetrathiomolybdate (TM) is a copper-depleting agent that has potential in treating copper-dependent diseases. Alvarez et al. (p. 331 , published online 26 November) used spectroscopic and structural studies to show that TM inhibits the yeast copper chaperone Atx1 by forming a TM-Cu-ATx1 complex that is stabilized by a sulfur-bridged copper-molybdenum cluster. Cluster formation prevents transfer of copper from the chaperone to target enzymes. The results provide a basis for developing drugs that target metallation pathways.

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