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Science 24 December 2004:
Vol. 306. no. 5705, pp. 2251 - 2255
DOI: 10.1126/science.1106289
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Reports

Dephosphorylation of the Calcium Pump Coupled to Counterion Occlusion

Claus Olesen,1* Thomas Lykke-Møller Sørensen,1* Rikke Christina Nielsen,1* Jesper Vuust Møller,2{dagger} Poul Nissen1{dagger}

P-type ATPases extract energy by hydrolysis of adenosine triphosphate (ATP) in two steps, formation and breakdown of a covalent phosphoenzyme intermediate. This process drives active transport and countertransport of the cation pumps. We have determined the crystal structure of rabbit sarcoplasmic reticulum Ca2+ adenosine triphosphatase in complex with aluminum fluoride, which mimics the transition state of hydrolysis of the counterion-bound (protonated) phosphoenzyme. On the basis of structural analysis and biochemical data, we find this form to represent an occluded state of the proton counterions. Hydrolysis is catalyzed by the conserved Thr-Gly-Glu-Ser motif, and it exploits an associative nucleophilic reaction mechanism of the same type as phosphoryl transfer from ATP. On this basis, we propose a general mechanism of occluded transition states of Ca2+ transport and H+ countertransport coupled to phosphorylation and dephosphorylation, respectively.

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



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: jvm{at}biophys.au.dk (J.V.M.); pn{at}mb.au.dk (P.N.)

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