Pumping ions.

1. This is a concise review of the field of ion pumping from the perspective of the authors. 2. The period covered spans the discovery of Na(+) and K(+) concentration gradients across animal cell membranes by Carl Schmidt in the 1850s, through the isolation of the Na(+) /K(+) -ATPase by Skou in 1957 (for which he was awarded the 1997 Nobel Prize in Chemistry), to the publication of the first crystal structure of the enzyme in 2007 and beyond. 3. Contributions of the authors' research group to the resolution of the questions of the mechanism of the allosteric role of ATP within the Na(+) /K(+) -ATPase reaction cycle and how protomeric versus diprotomeric states of the enzyme influence its kinetics are discussed within the context of the research field. 4. The results obtained indicate that the Na(+) /K(+) -ATPase has a single ATP binding site, which can be catalytic or allosteric in different parts of the enzyme's reaction cycle. 5. The long-running controversy over whether P-type ATPases function as protomers or diprotomers can be resolved in the case of the Na(+) /K(+) -ATPase by an ATP-induced dissociation of (αβ)(2) diprotomers into separate αβ protomers. 6. Kinetic data suggest that protein-protein interactions between the two αβ protomers within an (αβ)(2) diprotomer result in a much lower enzymatic turnover (i.e. a lower gear) when only one of the α-subunits of the diprotomer has bound ATP. The inactive αβ protomer within the diprotomer can be thought of as causing a drag on the active protomer. Clinical and Experimental Pharmacology and Physiology