MODIFICATION OF HISTIDINE UNCOUPLES COOPERATIVITY OF CALCIUM BINDING TO THE CA·MG·ATPase OF SARCOPLASMIC RETICULUM

Publisher Summary This chapter elaborates the transport of Ca into the Sarcoplasmic Reticulum (SR) by a Ca 2+ ·Mg 2+ · ATPase induced by enzyme activation in a mechanism that appears to be allosteric. The Ca 2+ binding is highly cooperative, and it has been suggested that a conformational change associated with the cooperativity is responsible for enzyme activation. The induction of cooperativity into the Ca 2+ binding mechanism follows the pK of a histidyl residue. It is reported that EFA modification does not prevent ATP binding and by using an iodoacetamine spin-label (ISL) to report conformational effects on the enzyme, changes are found that accompany both the binding of ATP and subsequent Ca 2+ binding are present in the EPR spectrum. Same conformational change may allow for the phosphorylation of the enzyme. It is not known that histidine is directly involved in coupling Ca 2+ to phosphorylation or is simply required for the structural integrity of segments of the enzyme that are associated with Ca 2+ site exposure.