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ACTA, a fluorescent analogue of thapsigargin, is a potent inhibitor and a conformational probe of skeletal muscle Ca 2+ ‐ATPase
Author(s) -
Procida Kristina,
Caspersen Casper,
Kromann Hasse,
Brøgger Christensen Søren,
Treiman Marek
Publication year - 1998
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/s0014-5793(98)01352-0
Subject(s) - thapsigargin , serca , endoplasmic reticulum , chemistry , atpase , fluorescence , biophysics , skeletal muscle , calcium atpase , intracellular , biochemistry , enzyme , biology , endocrinology , physics , quantum mechanics
Thapsigargin is a highly potent and selective inhibitor of sarco‐endoplasmic reticulum (SERCA) family of Ca 2+ ‐ATPases and a useful tool in research concerning the function of intracellular Ca 2+ stores. We describe here a novel fluorescent derivative (8‐ O ‐(4‐aminocinnamoyl)‐8‐ O ‐debutanoylthapsigargin, termed ACTA) of this compound, acting as a Ca 2+ ‐ATPase inhibitor with a potency approaching that of thapsigargin. Binding of ACTA to the skeletal muscle sarcoplasmic reticulum vesicles results in a strong fluorescence enhancement, approximately 66% of which depends on ACTA association with Ca 2+ ‐ATPase. This specific component of ACTA fluorescence is sensitive to the E 1 ‐E 2 conformational equilibrium of the pump. The combined properties of high potency and binding‐dependent fluorescence suggest ACTA to be a useful probe for a range of studies involving the SERCA class of ATPases.