ArticleJournal of molecular modeling2012
Substrate binding and translocation of the serotonin transporter studied by docking and molecular dynamics simulations.
Article in Journal of molecular modeling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 36 citations in OpenAlex.
- Membrane Transporter of Serotonin and Hypercholesterolemia in Children.International journal of molecular sciences · 2024Article
- The substrate import mechanism of the human serotonin transporter.Biophysical journal · 2022Article
- Article
- Aromatic Bromination Abolishes the Psychomotor Features and Pro-social Responses of MDMA ("Ecstasy") in Rats and Preserves Affinity for the Serotonin Transporter (SERT).Frontiers in pharmacology · 2019Article
- A multiscale computational modelling approach predicts mechanisms of female sex risk in the setting of arousal-induced arrhythmias.The Journal of physiology · 2017Article
- Structure and Dynamics Study of LeuT Using the Markov State Model and Perturbation Response Scanning Reveals Distinct Ion Induced Conformational States.The journal of physical chemistry. B · 2016Article
- Exploring the Inhibitory Mechanism of Approved Selective Norepinephrine Reuptake Inhibitors and Reboxetine Enantiomers by Molecular Dynamics Study.Scientific reports · 2016Article
- Monoamine transporters: insights from molecular dynamics simulations.Frontiers in pharmacology · 2015Review
- Computational and biochemical docking of the irreversible cocaine analog RTI 82 directly demonstrates ligand positioning in the dopamine transporter central substrate-binding site.The Journal of biological chemistry · 2014Article
- Comparative molecular dynamics simulations of mitogen-activated protein kinase-activated protein kinase 5.International journal of molecular sciences · 2014Article
- Mutational analysis of the high-affinity zinc binding site validates a refined human dopamine transporter homology model.PLoS computational biology · 2013Article
- Monoamine transporter structure, function, dynamics, and drug discovery: a computational perspective.The AAPS journal · 2012Review
- Article
- Synthesis, in vitro binding studies and docking of long-chain arylpiperazine nitroquipazine analogues, as potential serotonin transporter inhibitors.European journal of medicinal chemistry · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serotonin (5-HT) transporter (SERT) plays an important role in the termination of 5-HT-mediated neurotransmission by transporting 5-HT away from the synaptic cleft and into the presynaptic neuron. In addition, SERT is the main target for antidepressant drugs, including the selective serotonin reuptake inhibitors (SSRIs). The three-dimensional (3D) structure of SERT has not yet been determined, and little is known about the molecular mechanisms of substrate binding and transport, though such information is very important for the development of new antidepressant drugs. In this study, a homology model of SERT was constructed based on the 3D structure of a prokaryotic homologous leucine transporter (LeuT) (PDB id: 2A65). Eleven tryptamine derivates (including 5-HT) and the SSRI (S)-citalopram were docked into the putative substrate binding site, and two possible binding modes of the ligands were found. To study the conformational effect that ligand binding may have on SERT, two SERT-5-HT and two SERT-(S)-citalopram complexes, as well as the SERT apo structure, were embedded in POPC lipid bilayers and comparative molecular dynamics (MD) simulations were performed. Our results show that 5-HT in the SERT-5-HT(B) complex induced larger conformational changes in the cytoplasmic parts of the transmembrane helices of SERT than any of the other ligands. Based on these results, we suggest that the formation and breakage of ionic interactions with amino acids in transmembrane helices 6 and 8 and intracellular loop 1 may be of importance for substrate translocation.
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