Linked Life Data

19260734

Source:http://linkedlifedata.com/resource/pubmed/id/19260734

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-3-19
pubmed:abstractText
To characterize drug binding to the human ether-a-go-go related gene (hERG) channel, a synergic approach interplaying patch-clamp experiments and a docking study was developed. Mutations were introduced into concatenated dimers of the hERG channel that were assembled into a heterotetramer with mutated diagonal subunits. The binding affinities of three drugs (cisapride, terfenadine, and N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl]carbonyl]phenyl]methanesulfonamide dihydrochloride (E-4031, 1)) to a set of mutant channels were examined electrophysiologically to assess the involved residues, their number, and relative positions. Cisapride and 1 interacted with Tyr652 residues on adjacent subunits, while terfenadine interacted with Tyr652 residues on diagonal, but not on adjacent, subunits. Phe656 was involved in the binding of all three drugs, and Ser624 was found to be only involved in cisapride and 1. The docking models demonstrated that pi-pi and CH-pi interactions rather than cation-pi interaction play a key role in drug binding to the hERG channel.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1630-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Docking model of drug binding to the human ether-à-go-go potassium channel guided by tandem dimer mutant patch-clamp data: a synergic approach.
pubmed:affiliation
Discovery Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., Osaka 532-8686, Japan.
pubmed:publicationType
Journal Article