Linked Life Data

7577952

Source:http://linkedlifedata.com/resource/pubmed/id/7577952

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
41
pubmed:dateCreated
1995-12-14
pubmed:abstractText
Monoiodotyrosine margatoxin ([125I]MgTX) specifically and reversibly labels a maximum of 0.8 pmol of sites/mg of protein in purified rat brain synaptic plasma membrane vesicles with a dissociation constant of 0.1 pM under equilibrium binding conditions. This Kd value was confirmed by kinetic experiments (Kd of 0.07 pM), competition assays employing native margatoxin (MgTX) (Ki of 0.15 pM), and receptor saturation studies (Kd of 0.18 pM). Thus, this toxin represents the highest affinity, reversible radioligand for any membrane-bound receptor or ion channel described to date. [125I]MgTX binding in this system is modulated by charybdotoxin (Ki of 5 pM), kaliotoxin (Ki of 1.5 pM), and the agitoxins I and II (Ki's of 0.1 and 0.3 pM, respectively), in a noncompetitive manner. Moreover, alpha-dendrotoxin displayed a Ki value of 0.5 pM. Iberiotoxin was without any effect, suggesting that the receptor site is likely to be associated with a voltage-gated K+ channel complex. [125I]MgTX binding is inhibited by cations that are established blockers of voltage-dependent K+ channels (Ba2+, Ca2+, Cs+). The monovalent cations Na+ and K+ stimulate binding at low concentrations before producing complete inhibition as their concentrations are increased. Stimulation of binding results from an allosteric interaction that decreases Kd, whereas inhibition is due to an ionic strength effect. Affinity labeling of the binding site in rat brain synaptic plasma membranes employing [125I]MgTX and the bifunctional cross-linking reagent, disuccinimidyl suberate, causes specific and covalent incorporation of toxin into a glycoprotein of an apparent molecular weight (M(r)) of 74,000. Deglycosylation studies reveal an M(r) for the core polypeptide of the MgTX receptor of 63,000.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13627-34
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:7577952-Amino Acid Sequence, pubmed-meshheading:7577952-Animals, pubmed-meshheading:7577952-Binding, Competitive, pubmed-meshheading:7577952-Binding Sites, pubmed-meshheading:7577952-Brain, pubmed-meshheading:7577952-Cations, Monovalent, pubmed-meshheading:7577952-Cloning, Molecular, pubmed-meshheading:7577952-Escherichia coli, pubmed-meshheading:7577952-Female, pubmed-meshheading:7577952-Iodine Radioisotopes, pubmed-meshheading:7577952-Kinetics, pubmed-meshheading:7577952-Ligands, pubmed-meshheading:7577952-Male, pubmed-meshheading:7577952-Molecular Sequence Data, pubmed-meshheading:7577952-Molecular Weight, pubmed-meshheading:7577952-Neurotoxins, pubmed-meshheading:7577952-Peptide Fragments, pubmed-meshheading:7577952-Potassium Channels, pubmed-meshheading:7577952-Radioligand Assay, pubmed-meshheading:7577952-Rats, pubmed-meshheading:7577952-Rats, Wistar, pubmed-meshheading:7577952-Recombinant Proteins, pubmed-meshheading:7577952-Scorpion Venoms, pubmed-meshheading:7577952-Synaptic Membranes
pubmed:year
1995
pubmed:articleTitle
[125I]margatoxin, an extraordinarily high affinity ligand for voltage-gated potassium channels in mammalian brain.
pubmed:affiliation
Institute for Biochemical Pharmacology, Innsbruck, Austria.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't