Linked Life Data

15952239

Source:http://linkedlifedata.com/resource/pubmed/id/15952239

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5-6
pubmed:dateCreated
2005-6-22
pubmed:abstractText
We recently demonstrated that in the D4 dopamine receptor the aromatic microdomain that spans the interface of the second and third transmembrane (TM) domains influences the high affinity interactions of extremely D4-selective ligands possessing a 1,4-disubstituted aromatic piperazine/piperidine (1,4-DAP) structure. On the basis of their substructural features and patterns of sensitivity to mutations constructed in a D4 receptor background, the D4-selective 1,4-DAPs were categorized as having two distinct modes of binding that we named mode-1 and mode-3 [1]. Here we extend these findings of the ligand-receptor structure-affinity relationships for some of these highly D4-selective 1,4-DAPs by measuring the effect of the corresponding reciprocal TM2/TM3 mutations constructed in a D2 dopamine receptor background on the binding affinity of the para-halogenated mode-1 ligands L750,667 and FAUC213. The results indicate that the D2-V2.61F + FV3.28-3.29LM mutant binds L750,667 and FAUC213 with significantly increased affinity, i.e., its binding profile becomes more D4-like. These findings further support the assignment of the TM2/TM3 aromatic microdomain encompassing positions 2.61 and 3.28-3.29 as a 1,4-DAP D4-selectivity microdomain and highlights the importance of the precise emplacement of aromatics in this microdomain as key to the selective molecular recognition of L750,667 and FAUC213.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0365-6233
pubmed:author
pubmed:issnType
Print
pubmed:volume
338
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
268-75
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Reciprocal mutations in TM2/TM3 in a D2 dopamine receptor background confirms the importance of this microdomain as a selective determinant of para-halogenated 1,4-disubstituted aromatic piperazines.
pubmed:affiliation
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, 76107, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural