Source:http://linkedlifedata.com/resource/pubmed/id/10644729
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2000-2-29
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pubmed:databankReference | |
pubmed:abstractText |
This report describes the use of the concept of inversion of hydropathy patterns to the de novo design of peptides targeted to a predetermined site on a protein. Eight- and 12-residue peptides were constructed with the EF hands or Ca(2+)-coordinating sites of calmodulin as their anticipated points of interaction. These peptides, but not unrelated peptides nor those with the same amino acid composition but a scrambled sequence, interacted with the two carboxyl-terminal Ca(2+)-binding sites of calmodulin as well as the EF hands of troponin C. The interactions resulted in a conformational change whereby the 8-mer peptide-calmodulin complex could activate phosphodiesterase in the absence of Ca(2+). In contrast, the 12-mer peptide-calmodulin complex did not activate phosphodiesterase but rather inhibited activation by Ca(2+). This inhibition could be overcome by high levels of Ca(2+). Thus, it would appear that the aforementioned concept can be used to make peptide agonists and antagonists that are targeted to predetermined sites on proteins such as calmodulin.
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pubmed:grant | |
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 |
Jan
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2676-85
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10644729-Amino Acid Sequence,
pubmed-meshheading:10644729-Animals,
pubmed-meshheading:10644729-Calmodulin,
pubmed-meshheading:10644729-Cattle,
pubmed-meshheading:10644729-Drosophila,
pubmed-meshheading:10644729-Enzyme Activation,
pubmed-meshheading:10644729-Magnetic Resonance Spectroscopy,
pubmed-meshheading:10644729-Molecular Sequence Data,
pubmed-meshheading:10644729-Peptides,
pubmed-meshheading:10644729-Phosphoric Diester Hydrolases,
pubmed-meshheading:10644729-Protein Binding,
pubmed-meshheading:10644729-Protein Conformation,
pubmed-meshheading:10644729-Spectrometry, Fluorescence,
pubmed-meshheading:10644729-Surface Plasmon Resonance,
pubmed-meshheading:10644729-Troponin C
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pubmed:year |
2000
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pubmed:articleTitle |
De novo design of peptides targeted to the EF hands of calmodulin.
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pubmed:affiliation |
Department of Physiology, Cancer Center, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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