Mechanism of Ca2+ transport by Ca2+-Mg2+-ATPase pump: analysis of major states and pathways.
Mechanistic studies of Ca2+ transport by the Ca2+-Mg2+-ATPase of skeletal sarcoplasmic reticulum are reviewed, and a unifying model is proposed. The significant steps in the transport cycle are modeled in terms of occupation and disposition of three binding sites on the enzyme: a) two translocation sites capable of binding to Ca2+ or a charge-stoichiometric amount of alkali cation (M+) or H+, b) an ATP-ADP-binding site, and c) a phosphorylation or phosphate-binding site. The normal transport cycle is characterized as the following sequence of steps: a) binding of two Ca2+ and Mg-ATP to external sites with high affinity and random order, b) enzyme phosphorylation, c) inward translocation of the Ca2+-laden sites, d) Ca2+ release to the sarcoplasmic reticulum lumen and ADP release to the external medium (random order), e) binding of Mg2+ or a charge-stoichiometric amount of K+ plus H+ to the translocators, f) dephosphorylation, g) the return of the K+- and H+-laden translocators to the outside, and h) dissociation of K+ and H+ from the translocator and completion of the cycle with step a. The enzyme is characterized as a Ca2+-K+ plus H+ countertransporter. The K+ plus H+ remove Ca2+ from the inwardly oriented translocator, thereby relieving a product inhibition and increasing the rate of enzyme dephosphorylation.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001693:Biological Transport, Active; D017301:Ca(2+) Mg(2+)-ATPase; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002414:Cations, Monovalent; D004789:Enzyme Activation; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000378:metabolism*; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008954:Models, Biological; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D011522:Protons; D011817:Rabbits; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000201:enzymology
D002414:Cations, Monovalent; D007473:Ion Channels; D010761:Phosphorus Radioisotopes; D011522:Protons; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D011188:Potassium; D002118:Calcium