| pubmed-article:20392081 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20392081 | lifeskim:mentions | umls-concept:C0020792 | lld:lifeskim |
| pubmed-article:20392081 | lifeskim:mentions | umls-concept:C0006772 | lld:lifeskim |
| pubmed-article:20392081 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:20392081 | lifeskim:mentions | umls-concept:C0231491 | lld:lifeskim |
| pubmed-article:20392081 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:20392081 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:20392081 | lifeskim:mentions | umls-concept:C0871161 | lld:lifeskim |
| pubmed-article:20392081 | pubmed:issue | 19 | lld:pubmed |
| pubmed-article:20392081 | pubmed:dateCreated | 2010-5-11 | lld:pubmed |
| pubmed-article:20392081 | pubmed:abstractText | We developed a high-throughput yeast-based assay to screen for chemical inhibitors of Ca(2+)/calmodulin-dependent kinase pathways. After screening two small libraries, we identified the novel antagonist 125-C9, a substituted ethyleneamine. In vitro kinase assays confirmed that 125-C9 inhibited several calmodulin-dependent kinases (CaMKs) competitively with Ca(2+)/calmodulin (Ca(2+)/CaM). This suggested that 125-C9 acted as an antagonist for Ca(2+)/CaM rather than for CaMKs. We confirmed this hypothesis by showing that 125-C9 binds directly to Ca(2+)/CaM using isothermal titration calorimetry. We further characterized binding of 125-C9 to Ca(2+)/CaM and compared its properties with those of two well-studied CaM antagonists: trifluoperazine (TFP) and W-13. Isothermal titration calorimetry revealed that binding of 125-C9 to CaM is absolutely Ca(2+)-dependent, likely occurs with a stoichiometry of five 125-C9 molecules to one CaM molecule, and involves an exchange of two protons at pH 7.0. Binding of 125-C9 is driven overall by entropy and appears to be competitive with TFP and W-13, which is consistent with occupation of similar binding sites. To test the effects of 125-C9 in living cells, we evaluated mitogen-stimulated re-entry of quiescent cells into proliferation and found similar, although slightly better, levels of inhibition by 125-C9 than by TFP and W-13. Our results not only define a novel Ca(2+)/CaM inhibitor but also reveal that chemically unique CaM antagonists can bind CaM by distinct mechanisms but similarly inhibit cellular actions of CaM. | lld:pubmed |
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| pubmed-article:20392081 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20392081 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20392081 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20392081 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:20392081 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20392081 | pubmed:month | May | lld:pubmed |
| pubmed-article:20392081 | pubmed:issn | 1520-4995 | lld:pubmed |
| pubmed-article:20392081 | pubmed:author | pubmed-author:MeansAnthony... | lld:pubmed |
| pubmed-article:20392081 | pubmed:author | pubmed-author:TooneEric JEJ | lld:pubmed |
| pubmed-article:20392081 | pubmed:author | pubmed-author:ColomerJosepJ | lld:pubmed |
| pubmed-article:20392081 | pubmed:author | pubmed-author:SchmittAlliso... | lld:pubmed |
| pubmed-article:20392081 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20392081 | pubmed:day | 18 | lld:pubmed |
| pubmed-article:20392081 | pubmed:volume | 49 | lld:pubmed |
| pubmed-article:20392081 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20392081 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20392081 | pubmed:pagination | 4244-54 | lld:pubmed |
| pubmed-article:20392081 | pubmed:dateRevised | 2011-9-26 | lld:pubmed |
| pubmed-article:20392081 | pubmed:meshHeading | pubmed-meshheading:20392081... | lld:pubmed |
| pubmed-article:20392081 | pubmed:meshHeading | pubmed-meshheading:20392081... | lld:pubmed |
| pubmed-article:20392081 | pubmed:meshHeading | pubmed-meshheading:20392081... | lld:pubmed |
| pubmed-article:20392081 | pubmed:meshHeading | pubmed-meshheading:20392081... | lld:pubmed |
| pubmed-article:20392081 | pubmed:meshHeading | pubmed-meshheading:20392081... | lld:pubmed |
| pubmed-article:20392081 | pubmed:meshHeading | pubmed-meshheading:20392081... | lld:pubmed |
| pubmed-article:20392081 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20392081 | pubmed:articleTitle | Identification and inhibitory properties of a novel Ca(2+)/calmodulin antagonist. | lld:pubmed |
| pubmed-article:20392081 | pubmed:affiliation | Department of Pharmacology and Cancer Biology, Duke University Medical Center, P.O. Box 3813, Durham, North Carolina 27710, USA. | lld:pubmed |
| pubmed-article:20392081 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20392081 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:20392081 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
