Laboratorio de Fisico-Quimica Biologica, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal de Rio de Janeiro, 21949-900 Rio de Janeiro, Brazil-
Abstract: The pathogenesis of human Menkes and Wilson diseases depends on alterations in copper transport- Some reports suggest that intracellular traffic of copper might be regulated by kinase-mediated phosphorylation- However, there is no evidence showing the influence of kinase-related processes in coupled ATP hydrolysis-copper transport cycles- Here, we show that cyclic AMP-dependent protein kinase -PKA- regulates Ccc2p, the yeast Cu-I--ATPase, with PKA-mediated phosphorylation of a conserved serine -Ser258- being crucial for catalysis- Long-range intramolecular communication between Ser258 and Asp627 -at the catalytic site- modulates the key pumping event- the conversion of the high-energy to the low-energy phosphorylated intermediate associated with copper release-