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Science 11 June 2004:
Vol. 304. no. 5677, pp. 1672 - 1675
DOI: 10.1126/science.1099366
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Reports

Phosphoryl Transfer and Calcium Ion Occlusion in the Calcium Pump

Thomas Lykke-Møller Sørensen,1 Jesper Vuust Møller,2* Poul Nissen1*

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 (ß–{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~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.

1 Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
2 Department of Biophysics, University of Aarhus, Ole Worms Allé 185, DK-8000 Aarhus C, Denmark.

* To whom correspondence should be addressed. E-mail: jvm{at}biophys.au.dk (J.V.M.) and nissen{at}imsb.au.dk (P.N.)

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Highlights from the Literature.
(2004)
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Distinct Types of Abnormality in Kinetic Properties of Three Darier Disease-causing Sarco(endo)plasmic Reticulum Ca2+-ATPase Mutants That Exhibit Normal Expression and High Ca2+ Transport Activity.
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