METAL LIGAND-BINDING SPECIFICITIES OF THE TYROSINASE-RELATED PROTEINS

The production of pigment in mammalian melanocytes requires the intera ction of at least 3 melanogenic enzymes, which regulate the type and a mount of melanins produced. All 3 known enzymes belong to the TRP gene family and share many common structural features, including two metal binding domains thought to be important to their catalytic functions. This study used radiolabeled metal ligand binding with autoradiograph y as well as reconstitution protocols to analyze the binding of metal cations to these enzymes. The results demonstrate that all 3 enzymes a re capable of binding divalent metal cations; copper is bound to tyros inase but not to TRP1 or TRP2, TRP2 requires zinc as its metal ligand, and small amounts of iron bound to TRP2; TRP1 did not bind copper, zi nc or iron. Clearly, the specific binding of different metals by the T RPs is responsible for their distinct catalytic functions in melanogen esis. (C) 1998 Academic Press.