New Metalloprotein Cluster Discovered

Crystallographic analysis of tetrathiomolybdate (TM) interacting with the yeast metallochaperone protein Atx1 has revealed a copper-molybdenum cluster never before seen in metalloproteins (Science, DOI: 10.1126/science.1179907). Atx1 is related to the human protein Atox1, which forms a complex with Wilson disease protein in order to transfer copper. TM is used to inhibit several copper enzymes, but the structures of the complexes are not yet known. Thomas V. O’Halloran of Northwestern University and coworkers expected that TM would inhibit Atx1 by removing copper from its binding site and forming a polymeric copper-molybdenum sulfide precipitate. Instead, the copper remains in its binding site and forms part of a nest-shaped cluster that consists of four Cu⁺, a single MoS₄ ^2–, and three pairs of sulfur atoms from two Atx1 cysteines involved in copper binding. In a gel-based assay, the researchers show that TM inhibits Atx1’s copper chaperone activity.