Linked Life Data

8938722

Source:http://linkedlifedata.com/resource/pubmed/id/8938722

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1997-3-11
pubmed:abstractText
Charybdotoxin is a small peptide blocker of K+ channels, rigidly held in active conformation by three disulfide bonds. The toxin blocks K+ channels by binding to a receptor site located at the external "vestibule", and thus physically occluding the outer opening of the K+ conduction pore. In the blocked complex, K27, a residue on the toxin's molecular surface, projects its epsilon-amino group into the K(+)-selective pore. The results here show that CTX, produced by heterologous expression in E. coli, may be manipulated to place unnatural positively charged residues at position 27. The toxin folds faithfully to its native conformation when the crucial lysine at position 27 is replaced by a cysteine residue, a maneuver that allows specific chemical modification of this side-chain. Replacements of K27 by side-chains slightly shorter or slightly longer than lysine yield active toxins. The toxin variant with ornithine at this position interacts much less strongly with K+ ions in the pore of slowpoke-type Ca2(+)-activated K+ channels than does wild-type toxin. This result argues that the epsilon-amino group of K27 in bound toxin lies only a few ångstroms away from a K+ ion occupying the blocked pore. The peptide folds with high efficiency to form the correct disulfides even in the presence of strong denaturants.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
915-21
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Interaction of Ca2(+)-activated K+ channels with refolded charybdotoxins mutated at a central interaction residue.
pubmed:affiliation
Howard Hughes Medical Institute, Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't