Mapping the Binding Site for Escitalopram and Paroxetine in the Human Serotonin Transporter Using Genetically Encoded Photo-Cross-Linkers

Research output: Contribution to journalLetterResearchpeer-review

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Mapping the Binding Site for Escitalopram and Paroxetine in the Human Serotonin Transporter Using Genetically Encoded Photo-Cross-Linkers. / Rannversson, Hafsteinn; Andersen, Jacob; Bang-Andersen, Benny; Strømgaard, Kristian.

In: ACS chemical biology, Vol. 12, No. 10, 20.10.2017, p. 2558-2562.

Research output: Contribution to journalLetterResearchpeer-review

Harvard

Rannversson, H, Andersen, J, Bang-Andersen, B & Strømgaard, K 2017, 'Mapping the Binding Site for Escitalopram and Paroxetine in the Human Serotonin Transporter Using Genetically Encoded Photo-Cross-Linkers', ACS chemical biology, vol. 12, no. 10, pp. 2558-2562. https://doi.org/10.1021/acschembio.7b00338

APA

Rannversson, H., Andersen, J., Bang-Andersen, B., & Strømgaard, K. (2017). Mapping the Binding Site for Escitalopram and Paroxetine in the Human Serotonin Transporter Using Genetically Encoded Photo-Cross-Linkers. ACS chemical biology, 12(10), 2558-2562. https://doi.org/10.1021/acschembio.7b00338

Vancouver

Rannversson H, Andersen J, Bang-Andersen B, Strømgaard K. Mapping the Binding Site for Escitalopram and Paroxetine in the Human Serotonin Transporter Using Genetically Encoded Photo-Cross-Linkers. ACS chemical biology. 2017 Oct 20;12(10):2558-2562. https://doi.org/10.1021/acschembio.7b00338

Author

Rannversson, Hafsteinn ; Andersen, Jacob ; Bang-Andersen, Benny ; Strømgaard, Kristian. / Mapping the Binding Site for Escitalopram and Paroxetine in the Human Serotonin Transporter Using Genetically Encoded Photo-Cross-Linkers. In: ACS chemical biology. 2017 ; Vol. 12, No. 10. pp. 2558-2562.

Bibtex

@article{fe72ef722b2a4551b4bcd2a5eabf27c3,
title = "Mapping the Binding Site for Escitalopram and Paroxetine in the Human Serotonin Transporter Using Genetically Encoded Photo-Cross-Linkers",
abstract = "In spite of the important role of the human serotonin transporter (hSERT) in depression treatment, the molecular details of how antidepressant drugs bind are still not completely understood, in particular those related to potential high- and low-affinity binding sites in hSERT. Here, we utilize amber codon suppression in hSERT to encode the photo-cross-linking unnatural amino acid p-azido-l-phenylalanine into the suggested high- and low-affinity binding sites. We then employ UV-induced cross-linking with azF to map the binding site of escitalopram and paroxetine, two prototypical selective serotonin reuptake inhibitors (SSRIs). We find that the two antidepressant drugs exclusively cross-link to azF incorporated at the high-affinity binding site of hSERT, while cross-linking is not observed at the low-affinity binding site. Combined with previous homology models and recent structural data on hSERT, our results provide important information to understand the molecular details of these clinical relevant binding sites.",
keywords = "Binding Sites, Citalopram, Crystallography, X-Ray, Humans, Models, Molecular, Paroxetine, Protein Binding, Protein Conformation, Serotonin Plasma Membrane Transport Proteins, Serotonin Uptake Inhibitors, Journal Article",
author = "Hafsteinn Rannversson and Jacob Andersen and Benny Bang-Andersen and Kristian Str{\o}mgaard",
year = "2017",
month = "10",
day = "20",
doi = "10.1021/acschembio.7b00338",
language = "English",
volume = "12",
pages = "2558--2562",
journal = "A C S Chemical Biology",
issn = "1554-8929",
publisher = "American Chemical Society",
number = "10",

}

RIS

TY - JOUR

T1 - Mapping the Binding Site for Escitalopram and Paroxetine in the Human Serotonin Transporter Using Genetically Encoded Photo-Cross-Linkers

AU - Rannversson, Hafsteinn

AU - Andersen, Jacob

AU - Bang-Andersen, Benny

AU - Strømgaard, Kristian

PY - 2017/10/20

Y1 - 2017/10/20

N2 - In spite of the important role of the human serotonin transporter (hSERT) in depression treatment, the molecular details of how antidepressant drugs bind are still not completely understood, in particular those related to potential high- and low-affinity binding sites in hSERT. Here, we utilize amber codon suppression in hSERT to encode the photo-cross-linking unnatural amino acid p-azido-l-phenylalanine into the suggested high- and low-affinity binding sites. We then employ UV-induced cross-linking with azF to map the binding site of escitalopram and paroxetine, two prototypical selective serotonin reuptake inhibitors (SSRIs). We find that the two antidepressant drugs exclusively cross-link to azF incorporated at the high-affinity binding site of hSERT, while cross-linking is not observed at the low-affinity binding site. Combined with previous homology models and recent structural data on hSERT, our results provide important information to understand the molecular details of these clinical relevant binding sites.

AB - In spite of the important role of the human serotonin transporter (hSERT) in depression treatment, the molecular details of how antidepressant drugs bind are still not completely understood, in particular those related to potential high- and low-affinity binding sites in hSERT. Here, we utilize amber codon suppression in hSERT to encode the photo-cross-linking unnatural amino acid p-azido-l-phenylalanine into the suggested high- and low-affinity binding sites. We then employ UV-induced cross-linking with azF to map the binding site of escitalopram and paroxetine, two prototypical selective serotonin reuptake inhibitors (SSRIs). We find that the two antidepressant drugs exclusively cross-link to azF incorporated at the high-affinity binding site of hSERT, while cross-linking is not observed at the low-affinity binding site. Combined with previous homology models and recent structural data on hSERT, our results provide important information to understand the molecular details of these clinical relevant binding sites.

KW - Binding Sites

KW - Citalopram

KW - Crystallography, X-Ray

KW - Humans

KW - Models, Molecular

KW - Paroxetine

KW - Protein Binding

KW - Protein Conformation

KW - Serotonin Plasma Membrane Transport Proteins

KW - Serotonin Uptake Inhibitors

KW - Journal Article

U2 - 10.1021/acschembio.7b00338

DO - 10.1021/acschembio.7b00338

M3 - Letter

VL - 12

SP - 2558

EP - 2562

JO - A C S Chemical Biology

JF - A C S Chemical Biology

SN - 1554-8929

IS - 10

ER -

ID: 186909955