Structural basis of organic cation transporter-3 inhibition

Research output: Contribution to journal › Journal article › Research › peer-review

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Structural basis of organic cation transporter-3 inhibition. / Khanppnavar, Basavraj; Maier, Julian; Herborg, Freja; Gradisch, Ralph; Lazzarin, Erika; Luethi, Dino; Yang, Jae Won; Qi, Chao; Holy, Marion; Jäntsch, Kathrin; Kudlacek, Oliver; Schicker, Klaus; Werge, Thomas; Gether, Ulrik; Stockner, Thomas; Korkhov, Volodymyr M.; Sitte, Harald H.

In: Nature Communications, Vol. 13, No. 1, 6714, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Khanppnavar, B, Maier, J, Herborg, F, Gradisch, R, Lazzarin, E, Luethi, D, Yang, JW, Qi, C, Holy, M, Jäntsch, K, Kudlacek, O, Schicker, K, Werge, T, Gether, U, Stockner, T, Korkhov, VM & Sitte, HH 2022, 'Structural basis of organic cation transporter-3 inhibition', Nature Communications, vol. 13, no. 1, 6714. https://doi.org/10.1038/s41467-022-34284-8

APA

Khanppnavar, B., Maier, J., Herborg, F., Gradisch, R., Lazzarin, E., Luethi, D., Yang, J. W., Qi, C., Holy, M., Jäntsch, K., Kudlacek, O., Schicker, K., Werge, T., Gether, U., Stockner, T., Korkhov, V. M., & Sitte, H. H. (2022). Structural basis of organic cation transporter-3 inhibition. Nature Communications, 13(1), [6714]. https://doi.org/10.1038/s41467-022-34284-8

Vancouver

Khanppnavar B, Maier J, Herborg F, Gradisch R, Lazzarin E, Luethi D et al. Structural basis of organic cation transporter-3 inhibition. Nature Communications. 2022;13(1). 6714. https://doi.org/10.1038/s41467-022-34284-8

Author

Khanppnavar, Basavraj ; Maier, Julian ; Herborg, Freja ; Gradisch, Ralph ; Lazzarin, Erika ; Luethi, Dino ; Yang, Jae Won ; Qi, Chao ; Holy, Marion ; Jäntsch, Kathrin ; Kudlacek, Oliver ; Schicker, Klaus ; Werge, Thomas ; Gether, Ulrik ; Stockner, Thomas ; Korkhov, Volodymyr M. ; Sitte, Harald H. / Structural basis of organic cation transporter-3 inhibition. In: Nature Communications. 2022 ; Vol. 13, No. 1.

Bibtex

@article{1799ef47e5d445f0b4fedeb38268bad7,

title = "Structural basis of organic cation transporter-3 inhibition",

abstract = "Organic cation transporters (OCTs) facilitate the translocation of catecholamines, drugs and xenobiotics across the plasma membrane in various tissues throughout the human body. OCT3 plays a key role in low-affinity, high-capacity uptake of monoamines in most tissues including heart, brain and liver. Its deregulation plays a role in diseases. Despite its importance, the structural basis of OCT3 function and its inhibition has remained enigmatic. Here we describe the cryo-EM structure of human OCT3 at 3.2 {\AA} resolution. Structures of OCT3 bound to two inhibitors, corticosterone and decynium-22, define the ligand binding pocket and reveal common features of major facilitator transporter inhibitors. In addition, we relate the functional characteristics of an extensive collection of previously uncharacterized human genetic variants to structural features, thereby providing a basis for understanding the impact of OCT3 polymorphisms.",

author = "Basavraj Khanppnavar and Julian Maier and Freja Herborg and Ralph Gradisch and Erika Lazzarin and Dino Luethi and Yang, {Jae Won} and Chao Qi and Marion Holy and Kathrin J{\"a}ntsch and Oliver Kudlacek and Klaus Schicker and Thomas Werge and Ulrik Gether and Thomas Stockner and Korkhov, {Volodymyr M.} and Sitte, {Harald H.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

doi = "10.1038/s41467-022-34284-8",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

number = "1",

}

RIS

TY - JOUR

T1 - Structural basis of organic cation transporter-3 inhibition

AU - Khanppnavar, Basavraj

AU - Maier, Julian

AU - Herborg, Freja

AU - Gradisch, Ralph

AU - Lazzarin, Erika

AU - Luethi, Dino

AU - Yang, Jae Won

AU - Qi, Chao

AU - Holy, Marion

AU - Jäntsch, Kathrin

AU - Kudlacek, Oliver

AU - Schicker, Klaus

AU - Werge, Thomas

AU - Gether, Ulrik

AU - Stockner, Thomas

AU - Korkhov, Volodymyr M.

AU - Sitte, Harald H.

PY - 2022

Y1 - 2022

N2 - Organic cation transporters (OCTs) facilitate the translocation of catecholamines, drugs and xenobiotics across the plasma membrane in various tissues throughout the human body. OCT3 plays a key role in low-affinity, high-capacity uptake of monoamines in most tissues including heart, brain and liver. Its deregulation plays a role in diseases. Despite its importance, the structural basis of OCT3 function and its inhibition has remained enigmatic. Here we describe the cryo-EM structure of human OCT3 at 3.2 Å resolution. Structures of OCT3 bound to two inhibitors, corticosterone and decynium-22, define the ligand binding pocket and reveal common features of major facilitator transporter inhibitors. In addition, we relate the functional characteristics of an extensive collection of previously uncharacterized human genetic variants to structural features, thereby providing a basis for understanding the impact of OCT3 polymorphisms.

AB - Organic cation transporters (OCTs) facilitate the translocation of catecholamines, drugs and xenobiotics across the plasma membrane in various tissues throughout the human body. OCT3 plays a key role in low-affinity, high-capacity uptake of monoamines in most tissues including heart, brain and liver. Its deregulation plays a role in diseases. Despite its importance, the structural basis of OCT3 function and its inhibition has remained enigmatic. Here we describe the cryo-EM structure of human OCT3 at 3.2 Å resolution. Structures of OCT3 bound to two inhibitors, corticosterone and decynium-22, define the ligand binding pocket and reveal common features of major facilitator transporter inhibitors. In addition, we relate the functional characteristics of an extensive collection of previously uncharacterized human genetic variants to structural features, thereby providing a basis for understanding the impact of OCT3 polymorphisms.

U2 - 10.1038/s41467-022-34284-8

DO - 10.1038/s41467-022-34284-8

M3 - Journal article

C2 - 36344565

AN - SCOPUS:85141526608

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 6714

ER -

ID: 326841241

Department of Neuroscience