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Cyclic AMP‐dependent protein kinase controls energy interconversion during the catalytic cycle of the yeast copper‐ATPase
Author(s) -
Valverde Rafael H.F.,
Morin Isabelle,
Lowe Jennifer,
Mintz Elisabeth,
Cuillel Martine,
Vieyra Adalberto
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.02.022
Subject(s) - protein kinase a , phosphorylation , atpase , kinase , copper , yeast , intracellular , chemistry , biochemistry , serine , enzyme , microbiology and biotechnology , catalytic cycle , threonine , biology , biophysics , organic chemistry
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 (Ser 258 ) being crucial for catalysis. Long‐range intramolecular communication between Ser 258 and Asp 627 (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.