rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
11
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pubmed:dateCreated |
2006-6-7
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pubmed:abstractText |
We present crystal structures of the calcium-free E2 state of the sarcoplasmic reticulum Ca2+ -ATPase, stabilized by the inhibitor thapsigargin and the ATP analog AMPPCP. The structures allow us to describe the ATP binding site in a modulatory mode uncoupled from the Asp351 phosphorylation site. The Glu439 side chain interacts with AMPPCP via an Mg2+ ion in accordance with previous Fe2+ -cleavage studies implicating this residue in the ATPase cycle and in magnesium binding. Functional data on Ca2+ mediated activation indicate that the crystallized state represents an initial stage of ATP modulated deprotonation of E2, preceding the binding of Ca2+ ions in the membrane from the cytoplasmic side. We propose a mechanism of Ca2+ activation of phosphorylation leading directly from the compact E2-ATP form to the Ca2E1-ATP state. In addition, a role of Glu439 in ATP modulation of other steps of the functional cycle is suggested.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0261-4189
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2305-14
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16710301-Adenosine Triphosphate,
pubmed-meshheading:16710301-Animals,
pubmed-meshheading:16710301-Binding Sites,
pubmed-meshheading:16710301-Calcium,
pubmed-meshheading:16710301-Calcium-Transporting ATPases,
pubmed-meshheading:16710301-Crystallography, X-Ray,
pubmed-meshheading:16710301-Enzyme Activation,
pubmed-meshheading:16710301-Magnesium,
pubmed-meshheading:16710301-Models, Molecular,
pubmed-meshheading:16710301-Molecular Sequence Data,
pubmed-meshheading:16710301-Protein Structure, Tertiary,
pubmed-meshheading:16710301-Protons,
pubmed-meshheading:16710301-Rabbits,
pubmed-meshheading:16710301-Thapsigargin
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pubmed:year |
2006
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pubmed:articleTitle |
Modulatory and catalytic modes of ATP binding by the calcium pump.
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pubmed:affiliation |
Department of Molecular Biology, Aarhus University, Denmark.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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