Invited Symposium: SERCA-Type of Calcium Pumps and Phospholamban
Strock, C. (Dept. of Biochemistry and Molecular Biology, University of Maryland School of Medicine, USA)
Zhong, L. (Dept. of Biochemistry and Molecular Biology, University of Maryland School of Medicine, USA)
Kirtley, M.E. (Dept. of Biochemistry and Molecular Biology, University of Maryland School of Medicine, USA)
The SERCA ATPase is a 100,000 mw protein composed of a cytosolic globular region, connected through a stalk to a transmembrane region. This enzyme couples utilization of ATP to active transport of Ca2+ from the cytosol into membrane bound intracellular compartments ('Ca2+ stores'). The catalytic site, including the ATP binding domain and an aspartyl residue (Asp 351) which is phosphorylated as an intermediate step of ATP utilization, resides within the cytosolic globular region. Prior to ATP utilization, each enzyme molecule binds two Ca2+ (in exchange for H+) which are required for ATPase activation and are then transferred across the membrane as ATP is utilized. Mutational analysis indicates that the Ca2+ binding site resides within the transmembrane region. In fact, recent advances in recombinant enzyme production have permitted direct demonstration of Ca2+ binding defects following single site directed mutations on transmembrane helices. Similar experimentation suggests that the binding site for Thapsigargin (a highly specific inhibitor) is adjacent to the stalk (S3) segment. It is then apparent that the ATPase is an allosteric protein, and communication among catalytic, Ca2+ binding and Thapsigargin sites, occurs through long range intramolecular linkages.
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|Inesi, G.; Strock, C.; Zhong, L.; Kirtley, M.E.; (1998). Topology of Catalytic, Ca2+ Binding and Thapsigargin Sites, and Allosteric Character of the SERCA ATPase. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/wuytack/inesi0738/index.html|
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