Linked Life Data

18543980

Source:http://linkedlifedata.com/resource/pubmed/id/18543980

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2008-7-28
pubmed:abstractText
The reuptake of neurotransmitters by dopamine, norepinephrine, and serotonin transporters during neuronal transmission requires a sodium gradient. An "ionic mode" of binding proposes that aspartate anchors the ligand's positive charge but ignores the direct role of sodium in ligand binding seen in the only representative structure, the prokaryotic leucine transporter LeuT. Here, we built structural models of human transporters of dopamine, norepinephrine, and serotonin using the LeuT structure. The ligand and sodium-binding sites are highly conserved. We examined the possibilities for ligand binding given the available experimental evidence, including examples of catechol-cation chelates in X-ray structures of protein and other complexes. We conclude that a "chelation mode" of binding with direct interaction between the catechol hydroxyls and sodium is a valid alternative, with consequences for pharmaceutical design. In the modeled serotonin transporter complexes, Y95 is placed where it could select for serotonin through hydrogen bonding to the indole nitrogen.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1549-9596
pubmed:author
pubmed:issnType
Print
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1423-37
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Coordination of Na(+) by monoamine ligands in dopamine, norepinephrine, and serotonin transporters.
pubmed:affiliation
Department of Biochemistry and Pharmacy, Abo Akademi University, Tykistökatu 6 A, Turku, FI-20520 Finland. hxaard@abo.fi
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't