Linked Life Data

20660787

Source:http://linkedlifedata.com/resource/pubmed/id/20660787

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2010-8-11
pubmed:abstractText
An extensive search for isoflurane binding sites in the nicotinic acetylcholine receptor (nAChR) and the proton gated ion channel from Gloebacter violaceus (GLIC) has been carried out based on molecular dynamics (MD) simulations in fully hydrated lipid membrane environments. Isoflurane introduced into the aqueous phase readily partitions into the lipid membrane and the membrane-bound protein. Specifically, isoflurane binds persistently to three classes of sites in the nAChR transmembrane domain: (i) An isoflurane dimer occludes the pore, contacting residues identified by previous mutagenesis studies; analogous behavior is observed in GLIC. (ii) Several nAChR subunit interfaces are also occupied, in a site suggested by photoaffinity labeling and thought to positively modulate the receptor; these sites are not occupied in GLIC. (iii) Isoflurane binds to the subunit centers of both nAChR alpha chains and one of the GLIC chains, in a site that has had little experimental targeting. Interpreted in the context of existing structural and physiological data, the present MD results support a multisite model for the mechanism of receptor-channel modulation by anesthetics.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14122-7
pubmed:dateRevised
2010-9-9
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Multiple binding sites for the general anesthetic isoflurane identified in the nicotinic acetylcholine receptor transmembrane domain.
pubmed:affiliation
Institute for Computational and Molecular Science, Temple University, Philadelphia, PA 19122, USA. gbrannigan@temple.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural