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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2007-6-11
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pubmed:abstractText |
We have performed molecular dynamics simulations of a homology model of the human serotonin transporter (hSERT) in a membrane environment and in complex with either the natural substrate 5-HT or the selective serotonin reuptake inhibitor escitalopram. We have also included a transporter homologue, the Aquifex aeolicus leucine transporter (LeuT), in our study to evaluate the applicability of a simple and computationally attractive membrane system. Fluctuations in LeuT extracted from simulations are in good agreement with crystallographic B factors. Furthermore, key interactions identified in the X-ray structure of LeuT are maintained throughout the simulations indicating that our simple membrane system is suitable for studying the transmembrane protein hSERT in complex with 5-HT or escitalopram. For these transporter complexes, only relatively small fluctuations are observed in the ligand-binding cleft. Specific interactions responsible for ligand recognition, are identified in the hSERT-5HT and hSERT-escitalopram complexes. Our findings are in good agreement with predictions from mutagenesis studies.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1860-7187
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
827-40
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pubmed:meshHeading |
pubmed-meshheading:17436258-Bacterial Proteins,
pubmed-meshheading:17436258-Binding Sites,
pubmed-meshheading:17436258-Citalopram,
pubmed-meshheading:17436258-Computer Simulation,
pubmed-meshheading:17436258-Humans,
pubmed-meshheading:17436258-Leucine,
pubmed-meshheading:17436258-Models, Molecular,
pubmed-meshheading:17436258-Protein Binding,
pubmed-meshheading:17436258-Protein Interaction Mapping,
pubmed-meshheading:17436258-Serotonin,
pubmed-meshheading:17436258-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:17436258-Serotonin Uptake Inhibitors,
pubmed-meshheading:17436258-Sodium Chloride,
pubmed-meshheading:17436258-Solvents,
pubmed-meshheading:17436258-Thermodynamics,
pubmed-meshheading:17436258-Water
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pubmed:year |
2007
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pubmed:articleTitle |
Molecular dynamics simulations of Na+/Cl(-)-dependent neurotransmitter transporters in a membrane-aqueous system.
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pubmed:affiliation |
MEMPHYS-Center for Biomembrane Physics, Department of Chemistry, Technical University of Denmark, Building 206, 2800 Kgs. Lyngby, Denmark.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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