title: Molecular mechanism of the P-type ATPases.
abstract: The recent determination of the structure of the Ca2+-ATPase of sarcoplasmic reticulum to atomic resolution in the Ca2+-bound state and to near atomic resolution in the Ca2+-free, decavanadate-bound state has paved the way for an ultimate complete understanding of the molecular mechanism of the P-type ATPases. Analysis of this new structure information together with the large amount of biochemical information about these enzymes that preceded it has produced important new revelations about how the P-type ATPases work. Most models propose that these transporters operate by a strictly conformational energy coupling mechanism in which conformational changes in the large cytoplasmic head region mechanically drive the ions to be transported from their binding sites in the transmembrane helix region 50 A away. However, while these enzymes do indeed undergo profound conformational changes, the available evidence suggests that they do not mechanically transduce the chemical energy of ATP hydrolysis into transmembrane ion gradients via these conformational changes. As an alternative, it is proposed that the effects of the chemical events that occur at the phosphorylation/dephosphorylation site in the cytoplasmic region are exerted on the ion-binding sites via two well-defined charge transfer pathways that electronically connect the chemical reaction site with the site of ion binding. The recognition of these charge transfer pathways provides rational explanations of all of the key biochemical features of the P-type ATPase catalytic cycle. Thus, although a few details await elucidation, a nearly complete understanding of the P-type ATPase reaction mechanism may be at hand.
authors.affiliation: gas@med.unc.edu
authors.forename: Gene A
authors.initials: GA
authors.lastname: Scarborough
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D000252:Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism; D004735:Energy Transfer; D017136:Ion Transport; D008958:Models, Molecular; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism
chemical_list: D000251:Adenosine Triphosphatases; D006180:Proton-Translocating ATPases; D000252:Calcium-Transporting ATPases