Source:http://linkedlifedata.com/resource/pubmed/id/17504757
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
28
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| pubmed:dateCreated |
2007-7-9
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| pubmed:abstractText |
ATP binds to sarcoplasmic reticulum Ca(2+)-ATPase both in a phosphorylating (catalytic) mode and in a nonphosphorylating (modulatory) mode, the latter leading to acceleration of phosphoenzyme turnover (Ca(2)E(1)P --> E(2)P and E(2)P --> E(2) reactions) and Ca(2+) binding (E(2) --> Ca(2)E(1)). In some of the Ca(2+)-ATPase crystal structures, Arg(678) and Glu(439) seem to be involved in the binding of nucleotide or an associated Mg(2+) ion. We have replaced Arg(678), Glu(439), and Gly(438) with alanine to examine their importance for the enzyme cycle and the modulatory effects of ATP and MgATP. The results point to the key role of Arg(678) in nucleotide binding and to the importance of interdomain bonds Glu(439)-Ser(186) and Arg(678)-Asp(203) in stabilizing the E(2)P and E(2) intermediates, respectively. Mutation of Arg(678) had conspicuous effects on ATP/MgATP binding to the E(1) form and ADP binding to Ca(2)E(1)P, as well as ATP/MgATP binding in modulatory modes to E(2)P and E(2), whereas the effects on ATP/MgATP acceleration of the Ca(2)E(1)P --> E(2)P transition were small, suggesting that the nucleotide that accelerates Ca(2)E(1)P --> E(2)P binds differently from that modulating the E(2)P --> E(2) and E(2) --> Ca(2)E(1) reactions. Mutation of Glu(439) hardly affected nucleotide binding to E(1), Ca(2)E(1)P, and E(2), but it led to disruption of the modulatory effect of ATP on E(2)P --> E(2) and acceleration of the latter reaction, indicating that ATP normally modulates E(2)P --> E(2) by interfering with the interaction between Glu(439) and Ser(186). Gly(438) seems to be important for this interaction as well as for nucleotide binding, probably because of its role in formation of the helix containing Glu(439) and Thr(441).
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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 |
Jul
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
13
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| pubmed:volume |
282
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
20686-97
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| pubmed:meshHeading |
pubmed-meshheading:17504757-Adenosine Triphosphate,
pubmed-meshheading:17504757-Amino Acid Substitution,
pubmed-meshheading:17504757-Animals,
pubmed-meshheading:17504757-Catalysis,
pubmed-meshheading:17504757-Models, Chemical,
pubmed-meshheading:17504757-Models, Molecular,
pubmed-meshheading:17504757-Mutation, Missense,
pubmed-meshheading:17504757-Protein Binding,
pubmed-meshheading:17504757-Protein Structure, Secondary,
pubmed-meshheading:17504757-Rabbits,
pubmed-meshheading:17504757-Sarcoplasmic Reticulum,
pubmed-meshheading:17504757-Sarcoplasmic Reticulum Calcium-Transporting ATPases
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| pubmed:year |
2007
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| pubmed:articleTitle |
ATP-binding modes and functionally important interdomain bonds of sarcoplasmic reticulum Ca2+-ATPase revealed by mutation of glycine 438, glutamate 439, and arginine 678.
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| pubmed:affiliation |
Department of Physiology, Institute of Physiology and Biophysics, University of Aarhus, Ole Worms Allé 1160, DK-8000 Aarhus C, Denmark.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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