The application of vectorial coupling theory to the calcium pump

Models for the calcium pump of the E1E2 type appear to be inconsistent with new evidence for the binding of internal and external calcium ions, simultaneously, to the free pump. The models are shown here to be incomplete but not necessarily wrong; they omit the required modulation of the mobility, specificity, and enzyme activity of the pump, which is brought about through substrate-controlled conformational changes. A reaction scheme based on the E1E2 model but incorporating the conformational equilibria in question is shown to account for a variety of experimental findings, including those at odds with the simple model: (i) binding of lumenal Ca2+ to the free as well as the phosphorylated pump; (ii) uncoupled exit of lumenal Ca2+ at high concentrations; (iii) the absence of any effect of lumenal Ca2+ on the binding of external Ca2+; (iv) uncoupled ATPase activity in dimethyl sulfoxide.