The binding sites for cocaine and dopamine in the dopamine transporter overlap.

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

Standard

The binding sites for cocaine and dopamine in the dopamine transporter overlap. / Beuming, Thijs; Kniazeff, Julie; Bergmann, Marianne L; Shi, Lei; Gracia, Luis; Raniszewska, Klaudia; Newman, Amy Hauck; Javitch, Jonathan A; Weinstein, Harel; Gether, Ulrik; Løland, Claus Juul.

In: Nature Neuroscience, Vol. 11, No. 7, 2008, p. 780-9.

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

Harvard

Beuming, T, Kniazeff, J, Bergmann, ML, Shi, L, Gracia, L, Raniszewska, K, Newman, AH, Javitch, JA, Weinstein, H, Gether, U & Løland, CJ 2008, 'The binding sites for cocaine and dopamine in the dopamine transporter overlap.', Nature Neuroscience, vol. 11, no. 7, pp. 780-9. https://doi.org/10.1038/nn.2146

APA

Beuming, T., Kniazeff, J., Bergmann, M. L., Shi, L., Gracia, L., Raniszewska, K., Newman, A. H., Javitch, J. A., Weinstein, H., Gether, U., & Løland, C. J. (2008). The binding sites for cocaine and dopamine in the dopamine transporter overlap. Nature Neuroscience, 11(7), 780-9. https://doi.org/10.1038/nn.2146

Vancouver

Beuming T, Kniazeff J, Bergmann ML, Shi L, Gracia L, Raniszewska K et al. The binding sites for cocaine and dopamine in the dopamine transporter overlap. Nature Neuroscience. 2008;11(7):780-9. https://doi.org/10.1038/nn.2146

Author

Beuming, Thijs ; Kniazeff, Julie ; Bergmann, Marianne L ; Shi, Lei ; Gracia, Luis ; Raniszewska, Klaudia ; Newman, Amy Hauck ; Javitch, Jonathan A ; Weinstein, Harel ; Gether, Ulrik ; Løland, Claus Juul. / The binding sites for cocaine and dopamine in the dopamine transporter overlap. In: Nature Neuroscience. 2008 ; Vol. 11, No. 7. pp. 780-9.

Bibtex

@article{483b70f075ad11dd81b0000ea68e967b,
title = "The binding sites for cocaine and dopamine in the dopamine transporter overlap.",
abstract = "Cocaine is a widely abused substance with psychostimulant effects that are attributed to inhibition of the dopamine transporter (DAT). We present molecular models for DAT binding of cocaine and cocaine analogs constructed from the high-resolution structure of the bacterial transporter homolog LeuT. Our models suggest that the binding site for cocaine and cocaine analogs is deeply buried between transmembrane segments 1, 3, 6 and 8, and overlaps with the binding sites for the substrates dopamine and amphetamine, as well as for benztropine-like DAT inhibitors. We validated our models by detailed mutagenesis and by trapping the radiolabeled cocaine analog [3H]CFT in the transporter, either by cross-linking engineered cysteines or with an engineered Zn2+-binding site that was situated extracellularly to the predicted common binding pocket. Our data demonstrate the molecular basis for the competitive inhibition of dopamine transport by cocaine.",
author = "Thijs Beuming and Julie Kniazeff and Bergmann, {Marianne L} and Lei Shi and Luis Gracia and Klaudia Raniszewska and Newman, {Amy Hauck} and Javitch, {Jonathan A} and Harel Weinstein and Ulrik Gether and L{\o}land, {Claus Juul}",
year = "2008",
doi = "10.1038/nn.2146",
language = "English",
volume = "11",
pages = "780--9",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "nature publishing group",
number = "7",

}

RIS

TY - JOUR

T1 - The binding sites for cocaine and dopamine in the dopamine transporter overlap.

AU - Beuming, Thijs

AU - Kniazeff, Julie

AU - Bergmann, Marianne L

AU - Shi, Lei

AU - Gracia, Luis

AU - Raniszewska, Klaudia

AU - Newman, Amy Hauck

AU - Javitch, Jonathan A

AU - Weinstein, Harel

AU - Gether, Ulrik

AU - Løland, Claus Juul

PY - 2008

Y1 - 2008

N2 - Cocaine is a widely abused substance with psychostimulant effects that are attributed to inhibition of the dopamine transporter (DAT). We present molecular models for DAT binding of cocaine and cocaine analogs constructed from the high-resolution structure of the bacterial transporter homolog LeuT. Our models suggest that the binding site for cocaine and cocaine analogs is deeply buried between transmembrane segments 1, 3, 6 and 8, and overlaps with the binding sites for the substrates dopamine and amphetamine, as well as for benztropine-like DAT inhibitors. We validated our models by detailed mutagenesis and by trapping the radiolabeled cocaine analog [3H]CFT in the transporter, either by cross-linking engineered cysteines or with an engineered Zn2+-binding site that was situated extracellularly to the predicted common binding pocket. Our data demonstrate the molecular basis for the competitive inhibition of dopamine transport by cocaine.

AB - Cocaine is a widely abused substance with psychostimulant effects that are attributed to inhibition of the dopamine transporter (DAT). We present molecular models for DAT binding of cocaine and cocaine analogs constructed from the high-resolution structure of the bacterial transporter homolog LeuT. Our models suggest that the binding site for cocaine and cocaine analogs is deeply buried between transmembrane segments 1, 3, 6 and 8, and overlaps with the binding sites for the substrates dopamine and amphetamine, as well as for benztropine-like DAT inhibitors. We validated our models by detailed mutagenesis and by trapping the radiolabeled cocaine analog [3H]CFT in the transporter, either by cross-linking engineered cysteines or with an engineered Zn2+-binding site that was situated extracellularly to the predicted common binding pocket. Our data demonstrate the molecular basis for the competitive inhibition of dopamine transport by cocaine.

U2 - 10.1038/nn.2146

DO - 10.1038/nn.2146

M3 - Journal article

C2 - 18568020

VL - 11

SP - 780

EP - 789

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 7

ER -

ID: 5772580