Linked Life Data

8662820

Source:http://linkedlifedata.com/resource/pubmed/id/8662820

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
1996-8-26
pubmed:abstractText
The acetylcholine (ACh) receptors in muscle have the composition alpha2betagammadelta and contain two ACh binding sites. One is formed between an alpha subunit and the gamma subunit, and the other is formed between an alpha subunit and the delta subunit. Among the residues in the ACh binding sites are alphaCys-192 and alphaCys-193. The negatively charged deltaAsp-180 is at an appropriate distance from alphaCys-192/193 also to be in the ACh binding site and to interact electrostatically with the positively charged ammonium group common to agonists and competitive antagonists. Mutation to Asn of either deltaAsp-180 or the aligned residue in the gamma subunit, gammaAsp-174, decreased the affinities of three agonists, acetylcholine, tetramethylammonium, and succinyldicholine 170-560-fold. By contrast, these mutations decreased the affinities of three competitive antagonists, (+)-tubocurarine, hexamethonium, and dihydro-beta-erythroidine, only 2-15-fold. Agonists, but not antagonists, promote the transitions of the receptor from the resting state to the higher affinity active and desensitized states, and the greater effects of the mutations of gammaAsp-174 and deltaAsp-180 on the apparent affinities of agonists could reflect the involvement of these residues in the conformational changes of the receptor corresponding to its transitions to higher affinity states. In these transitions, one possibility is that gammaAsp-174 and deltaAsp-180 move closer to bound agonist.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13497-503
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
The contributions of aspartyl residues in the acetylcholine receptor gamma and delta subunits to the binding of agonists and competitive antagonists.
pubmed:affiliation
Center for Molecular Recognition, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't