Source:http://linkedlifedata.com/resource/pubmed/id/11684144
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2001-10-30
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| pubmed:abstractText |
The characterization of conantokin-T (con-T), conantokin-R (con-R), and variants thereof, using the whole-cell patch clamp technique, was undertaken to evaluate the contribution of various residues towards the onset and recovery of N-methyl-D-aspartate (NMDA) receptor inhibition in cultured embryonic murine hippocampal neurons. The results obtained indicate that the two most C-terminal gamma-carboxyglutamic acid (Gla) residues of the conantokins, while not essential for activity, provided for more tenacious binding to the receptor. Specifically, con-T[gamma10K/gamma14K] and con-R[gamma11A/gamma15A] displayed 5.6- and 8.4-fold decreases in tau(off), respectively, compared to the parent peptides. For the truncated con-T variants, con-T[1-9/Q6G], and a sarcosine (Src)-containing species, con-T[1-9/G1Src/Q6G], the tau(off) was over 80- and 40-fold faster, respectively, compared to con-T. For the latter peptide, the coapplication of 300 microM spermine enhanced the onset rate constant from 3.1x10(3)M(-1) x s(-1) to 12.6x10(3)M(-1) x s(-1). From analysis of equilibrium dose-inhibition curves using the Cheng-Prusoff equation, a K(i) value of 1.1 microM for the peptide was obtained. Con-T[1-9/G1Src/Q6G] demonstrated an apparent competitive mode of inhibition relative to NMDA. Schild analysis of the data yielded an equilibrium dissociation constant of 2.4 microM for the interaction of con-T[1-9/G1Src/Q6G] with the receptor.
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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/Conotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Mollusk Venoms,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Spermine,
http://linkedlifedata.com/resource/pubmed/chemical/conantokin R,
http://linkedlifedata.com/resource/pubmed/chemical/conantokin-T
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0028-3908
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
41
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
801-10
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11684144-Amino Acid Sequence,
pubmed-meshheading:11684144-Amino Acid Substitution,
pubmed-meshheading:11684144-Animals,
pubmed-meshheading:11684144-Binding, Competitive,
pubmed-meshheading:11684144-Cells, Cultured,
pubmed-meshheading:11684144-Conotoxins,
pubmed-meshheading:11684144-Excitatory Amino Acid Agonists,
pubmed-meshheading:11684144-Excitatory Amino Acid Antagonists,
pubmed-meshheading:11684144-Fetus,
pubmed-meshheading:11684144-Hippocampus,
pubmed-meshheading:11684144-Kinetics,
pubmed-meshheading:11684144-Mice,
pubmed-meshheading:11684144-Molecular Sequence Data,
pubmed-meshheading:11684144-Mollusk Venoms,
pubmed-meshheading:11684144-Neurons,
pubmed-meshheading:11684144-Peptide Fragments,
pubmed-meshheading:11684144-Peptides,
pubmed-meshheading:11684144-Protein Binding,
pubmed-meshheading:11684144-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:11684144-Spermine
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| pubmed:year |
2001
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| pubmed:articleTitle |
Kinetic and mechanistic characterization of NMDA receptor antagonism by replacement and truncation variants of the conantokin peptides.
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| pubmed:affiliation |
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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