title: Phosphoryl transfer and calcium ion occlusion in the calcium pump.
abstract: A tight coupling between adenosine triphosphate (ATP) hydrolysis and vectorial ion transport has to be maintained by ATP-consuming ion pumps. We report two crystal structures of Ca2+-bound sarco(endo)plasmic reticulum Ca2+-adenosine triphosphatase (SERCA) at 2.6 and 2.9 angstrom resolution in complex with (i) a nonhydrolyzable ATP analog [adenosine (beta-gamma methylene)-triphosphate] and (ii) adenosine diphosphate plus aluminum fluoride. SERCA reacts with ATP by an associative mechanism mediated by two Mg2+ ions to form an aspartyl-phosphorylated intermediate state (Ca2-E1 approximately P). The conformational changes that accompany the reaction with ATP pull the transmembrane helices 1 and 2 and close a cytosolic entrance for Ca2+, thereby preventing backflow before Ca2+ is released on the other side of the membrane.
authors.affiliation: Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
authors.forename: Thomas Lykke-Møller
authors.initials: TL
authors.lastname: Sørensen
authors.forename: Jesper Vuust
authors.initials: JV
authors.lastname: Møller
authors.forename: Poul
authors.initials: P
authors.lastname: Nissen
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism*; D017607:Aluminum Compounds / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000737:chemistry* / Q000378:metabolism*; D003460:Crystallization; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000378:metabolism; D005459:Fluorides / Q000378:metabolism; D008958:Models, Molecular; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology*; D010766:Phosphorylation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011817:Rabbits; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
chemical_list: D017607:Aluminum Compounds; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D005459:Fluorides; D002118:Calcium; C032311:aluminum fluoride