The serotonin (5-hydroxytryptamine, 5-HT) 5-HT G protein-coupled receptor (GPCR) family consists of types 2A, 2B, and 2C that share ~75% transmembrane (TM) sequence identity. Agonists for 5-HT receptors are under development for psychoses, whereas, at 5-HT receptors, antipsychotic effects are associated with antagonists-in fact, 5-HT agonists can cause hallucinations and 5-HT agonists cause cardiotoxicity. It is known that 5-HT TM6 residues W6.48, F6.51, and F6.52 impact ligand binding and function, however, ligand interactions with these residues at the 5-HT receptor has not been reported. To predict and validate molecular determinants for 5-HT-specific activation, results from receptor homology modeling, ligand docking, and molecular dynamics (MD) simulation studies were compared with experimental results for ligand binding and function at wild type and W6.48A, F6.51A, and F6.52A point-mutated 5-HT receptors.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979624 | PMC |
| http://dx.doi.org/10.1080/00268976.2013.833656 | DOI Listing |
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