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FEBS Lett. Mar (2008); 582(6):891-5
Cyclic AMP-dependent protein kinase controls energy interconversion during the catalytic cycle of the yeast copper-ATPase-
Valverde RH, Morin I, Lowe J, Mintz E, Cuillel M, Vieyra A
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-
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Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers.
Nucleic Acids Res. Jan 1;34:D535-9.