| pubmed-article:12124273 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12124273 | lifeskim:mentions | umls-concept:C0036248 | lld:lifeskim |
| pubmed-article:12124273 | lifeskim:mentions | umls-concept:C0005456 | lld:lifeskim |
| pubmed-article:12124273 | lifeskim:mentions | umls-concept:C0475264 | lld:lifeskim |
| pubmed-article:12124273 | lifeskim:mentions | umls-concept:C0439799 | lld:lifeskim |
| pubmed-article:12124273 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:12124273 | pubmed:dateCreated | 2002-7-18 | lld:pubmed |
| pubmed-article:12124273 | pubmed:abstractText | Saxitoxin (STX) selectively blocks the voltage-gated sodium channel at the outer vestibule lined by P-loops of the four domains. Neosaxitoxin has an additional -OH group at the N1 position of the 1,2,3 guanidinium (N1-OH) that interacts with domains I and IV of the Na(+) channel. Determination of a second toxin interaction with the channel would fix the location of STX. Gonyautoxin 2,3 and Gonyautoxin 1,4 are C-11 sulfated derivatives of saxitoxin and neosaxitoxin, respectively. We used these variants to constrain the STX docking orientation by energetically localizing the C-11 sulfate in the outer vestibule. Interactions between the C-11 sulfate and each of the four domains of the channel were determined by a systematic approach to mutant cycle analysis in which all known carboxyl groups important for site 1 toxin binding were neutralized, allowing energetic triangulation of the toxin sulfate and overcoming some limitations of mutant cycles. Toxin IC(50)s were measured by two-electrode voltage clamp from Xenopus oocytes injected with the channel mRNA. Three unique types of analysis based on the coupling results localized the C-11 sulfate between domains III and IV. Combined with our previous report, the data establish the orientation of STX in the outer vestibule and confirm the clockwise arrangement of the channel domains. | lld:pubmed |
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| pubmed-article:12124273 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12124273 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12124273 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12124273 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:12124273 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12124273 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:12124273 | pubmed:issn | 0006-3495 | lld:pubmed |
| pubmed-article:12124273 | pubmed:author | pubmed-author:LiXiufengX | lld:pubmed |
| pubmed-article:12124273 | pubmed:author | pubmed-author:ChoudharyGaur... | lld:pubmed |
| pubmed-article:12124273 | pubmed:author | pubmed-author:DudleySamuel... | lld:pubmed |
| pubmed-article:12124273 | pubmed:author | pubmed-author:ShangLisaL | lld:pubmed |
| pubmed-article:12124273 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12124273 | pubmed:volume | 83 | lld:pubmed |
| pubmed-article:12124273 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12124273 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12124273 | pubmed:pagination | 912-9 | lld:pubmed |
| pubmed-article:12124273 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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| pubmed-article:12124273 | pubmed:meshHeading | pubmed-meshheading:12124273... | lld:pubmed |
| pubmed-article:12124273 | pubmed:year | 2002 | lld:pubmed |
| pubmed-article:12124273 | pubmed:articleTitle | Energetic localization of saxitoxin in its channel binding site. | lld:pubmed |
| pubmed-article:12124273 | pubmed:affiliation | Department of Medicine, Emory University and Atlanta Veterans Administration Medical Center, Atlanta, Georgia 30322 USA. | lld:pubmed |
| pubmed-article:12124273 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12124273 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:12124273 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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