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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
46
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pubmed:dateCreated |
1994-12-21
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pubmed:abstractText |
We have studied the effects of cyclopiazonic acid (CPA) and halothane on the enzymatic activity, oligomeric state, and conformational equilibrium of the Ca-ATPase in skeletal muscle sarcoplasmic reticulum (SR). CPA is a potent inhibitor of Ca-ATPase activity, and this inhibition is competitive with respect to ATP concentration. Time-resolved phosphorescence anisotropy was used to detect the fraction of Ca-ATPase monomers, dimers, and larger aggregates in the absence and presence of CPA. CPA increased the fraction of dimers and larger aggregates of the Ca-ATPase. Addition of halothane to SR, or detergent solubilization of the Ca-ATPase, increased the apparent KI of CPA inhibition, and increased the fraction of Ca-ATPase present as monomers. CPA stabilized the E2 conformational state of the Ca-ATPase relative to the E1 and E2-P states, as measured by fluorescein 5-isothiocyanate fluorescence and enzyme phosphorylation from inorganic phosphate. E2-P formation in the presence of CPA was partially restored by halothane and solubilization. We conclude that CPA inhibits the Ca-ATPase in part by overstabilizing dimers or small oligomers of the Ca-ATPase, which is correlated with stabilization of the E2 conformation of the enzyme.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Transporting ATPases,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescein-5-isothiocyanate,
http://linkedlifedata.com/resource/pubmed/chemical/Halothane,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/cyclopiazonic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13928-37
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:7947799-Animals,
pubmed-meshheading:7947799-Calcium,
pubmed-meshheading:7947799-Calcium-Transporting ATPases,
pubmed-meshheading:7947799-Fluorescein-5-isothiocyanate,
pubmed-meshheading:7947799-Fluorescence Polarization,
pubmed-meshheading:7947799-Halothane,
pubmed-meshheading:7947799-Indoles,
pubmed-meshheading:7947799-Membrane Fluidity,
pubmed-meshheading:7947799-Membrane Lipids,
pubmed-meshheading:7947799-Phosphates,
pubmed-meshheading:7947799-Phosphorylation,
pubmed-meshheading:7947799-Rabbits,
pubmed-meshheading:7947799-Sarcoplasmic Reticulum,
pubmed-meshheading:7947799-Structure-Activity Relationship
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pubmed:year |
1994
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pubmed:articleTitle |
Halothane and cyclopiazonic acid modulate Ca-ATPase oligomeric state and function in sarcoplasmic reticulum.
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pubmed:affiliation |
Department of Biochemistry, University of Minnesota Medical School, Minneapolis 55455.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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