Linked Life Data

8913348

Source:http://linkedlifedata.com/resource/pubmed/id/8913348

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1996-12-26
pubmed:databankReference
pubmed:abstractText
Three 35-amino acid peptide K+ channel toxins (pandinotoxins) were purified from the venom of the scorpion Pandinus imperaton the toxins are designated pandinotoxin (PiTX)-K alpha, PiTX-K beta, and PiTX-K gamma. In an 86Rb tracer flux assay on rat brain synaptosomes, all three toxins selectively blocked the component of the K(+)-stimulated 86Rb efflux that corresponds to a voltage-gated, rapidly inactivating (A-type) K+ current (IC50 = 6, 42, and 100 nM, respectively). These toxins blocked neither the noninactivating component of the K(+)-stimulated 86Rb efflux (corresponding to a delayed rectifier) nor the Ca(2+)-dependent component of the 86Rb efflux (i.e., a Ca(2+)-activated K+ current) in these terminals. PiTX-K alpha, which was expressed by recombinant methods, also blocked the Kv1.2 channel expressed in fibroblasts (IC50 = 32 pM). PiTX-K alpha and PiTX-K beta have identical amino acid sequences except for the seventh amino acid: a proline in PiTX-K alpha, and a glutamic acid in PiTX-K beta. They have substantial sequence homology, especially at the carboxyl termini, with another scorpion toxin, charybdotoxin (ChTX), which blocks both the Ca(2+)-activated and the rapidly inactivating. K(+)-stimulated 86Rb efflux components in synaptosomes and the Kv 1.2 channel PiTX-K gamma, however, has much less sequence homology. Conserved in all four toxins are three identically positioned disulfide bridges; an asparagine at position 30; and positive charges at positions 27, 31, and 34 (based on ChTX numbering). PiTX-K gamma is novel in that it has a fourth pair of cysteines. The PiTX structures were computer simulated, using ChTX as a model. We speculate that the three-dimensional structures of all three PiTXs resemble that of ChTX: a beta-sheet at the carboxyl terminus, containing three cysteines, is linked to the central alpha-helix by two disulfide bridges (C17-C35 and C13-C33) and to an extended amino-terminal fragment by the third disulfide bridge (C7-C28). Further analysis of the three-dimensional structures reveals differences that may help to explain the selectivity and affinity differences of these toxins.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1167-77
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Three new toxins from the scorpion Pandinus imperator selectively block certain voltage-gated K+ channels.
pubmed:affiliation
Department of Physiology, School of Medicine, University of Maryland, Baltimore 21201, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't