ArticleNature communications2016
Genetically encoded photocrosslinkers locate the high-affinity binding site of antidepressant drugs in the human serotonin transporter.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
- In situ cell-surface conformation of the TCR-CD3 signaling complex.EMBO reports · 2024Article
- Noncanonical Amino Acid Tools and Their Application to Membrane Protein Studies.Chemical reviews · 2024Review
- Large-scale, in-cell photocrosslinking at single-residue resolution reveals the molecular basis for glucocorticoid receptor regulation by immunophilins.Nature structural & molecular biology · 2023Article
- Genetic code expansion to enable site-specific bioorthogonal labeling of functional G protein-coupled receptors in live cells.Protein science : a publication of the Protein Society · 2023Article
- Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins.Open life sciences · 2023Review
- Hydrophobic cavity-directed azide-acetyllysine photochemistry for profiling non-histone interacting partners of bromodomain protein 1.RSC chemical biology · 2022Article
- Molecular docking and biochemical validation of (-)-syringaresinol-4-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside binding to an allosteric site in monoamine transporters.Frontiers in pharmacology · 2022Article
- Engineered Human Induced Pluripotent Cells Enable Genetic Code Expansion in Brain Organoids.Chembiochem : a European journal of chemical biology · 2021Article
- High-throughput characterization of photocrosslinker-bearing ion channel variants to map residues critical for function and pharmacology.PLoS biology · 2021Article
- The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter.Nature communications · 2021Article
- Photosensitive tyrosine analogues unravel site-dependent phosphorylation in TrkA initiated MAPK/ERK signaling.Communications biology · 2020Article
- Capturing Peptide-GPCR Interactions and Their Dynamics.Molecules (Basel, Switzerland) · 2020Review
- Site-Specific Incorporation of Genetically Encoded Photo-Crosslinkers Locates the Heteromeric Interface of a GPCR Complex in Living Cells.Cell chemical biology · 2020Article
- Chemical modification of proteins by insertion of synthetic peptides using tandem protein trans-splicing.Nature communications · 2020Article
- Mechanism and site of action of big dynorphin on ASIC1a.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Using genetically incorporated unnatural amino acids to control protein functions in mammalian cells.Essays in biochemistry · 2019Review
- Therapeutic applications of genetic code expansion.Synthetic and systems biotechnology · 2018Review
- Playing with the Molecules of Life.ACS chemical biology · 2018Review
- Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells.Journal of visualized experiments : JoVE · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the well-established role of the human serotonin transporter (hSERT) in the treatment of depression, the molecular details of antidepressant drug binding are still not fully understood. Here we utilize amber codon suppression in a membrane-bound transporter protein to encode photocrosslinking unnatural amino acids (UAAs) into 75 different positions in hSERT. UAAs are incorporated with high specificity, and functionally active transporters have similar transport properties and pharmacological profiles compared with wild-type transporters. We employ ultraviolet-induced crosslinking with p-azido-L-phenylalanine (azF) at selected positions in hSERT to map the binding site of imipramine, a prototypical tricyclic antidepressant, and vortioxetine, a novel multimodal antidepressant. We find that the two antidepressants crosslink with azF incorporated at different positions within the central substrate-binding site of hSERT, while no crosslinking is observed at the vestibular-binding site. Taken together, our data provide direct evidence for defining the high-affinity antidepressant binding site in hSERT.
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