Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5-6
|
| pubmed:dateCreated |
1992-10-7
|
| pubmed:abstractText |
6-Epitetrodotoxin (6-epiTTX) and 11-deoxytetrodotoxin (11-deoxyTTX), isolated from an Okinawan newt, Cynops ensicauda, were tested for sodium-channel blocking effects on the voltage-clamped frog skeletal muscle fiber. In 6-epiTTX, the C-6 -OH is in an epimeric position; in 11-deoxyTTX, C-11 has a methyl in place of a hydroxymethyl group. At pH 7.25, the ED50s for reducing INa are: 4.1 nM (TTX), 96 nM (6-epiTTX), and 445 nM (11-deoxyTTX). In each analogue, the lowered potency can be attributed energetically to the loss of a hydrogen bond. By complementarity, in the sodium-channel receptor for TTX, there must be a hydrogen-acceptor group for the C-6 -OH, and another for the C-11 -OH. Therefore, the TTX molecule is bound to the receptor through an ion-pair (for the guanidinium), and five hydrogen bonds, one each for the -OH on C-9, C-10, C-4, and, as now identified, for C-6 and C-11. Considering the three-dimensional structure of the toxin molecules, these binding sites must be located in a fold or a crevice of the channel protein. If glutamate 387 of rat brain sodium channel II is the ion-pairing site for the guanidinium group, then the carbonyl oxygen of asparagine 388 is the hydrogen acceptor for the C-9 and C-10 -OHs.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0041-0101
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
30
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
635-43
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading | |
| pubmed:articleTitle |
Actions of 6-epitetrodotoxin and 11-deoxytetrodotoxin on the frog skeletal muscle fiber.
|
| pubmed:affiliation |
Department of Pharmacology, State University of New York, Brooklyn 11203.
|
| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|