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

Nature Neuroscience

Volumn 11, Issue 7, 2008, Pages 780-789

  Beuming, Thijs ^a   Kniazeff, Julie ^b   Bergmann, Marianne L ^b   Shi, Lei ^a   Gracia, Luis ^a   Raniszewska, Klaudia ^b   Newman, Amy Hauck ^c   Javitch, Jonathan A ^d   Weinstein, Harel ^a   Gether, Ulrik ^b   Loland, Claus J ^b  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c NATIONAL INSTITUTE ON DRUG ABUSE   (United States)

^d Columbia University ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPHETAMINE; BACTERIAL TRANSPORTER; BENZATROPINE; CARRIER PROTEIN; COCAINE; COCAINE DERIVATIVE; CYSTEINE; DOPAMINE TRANSPORTER; DOPAMINE TRANSPORTER PROTEIN INHIBITOR; JHW 007; PROTEIN LEUT; ZINC ION;

ANIMAL CELL; ARTICLE; BACTERIUM TRANSDUCTION; COCAINE DEPENDENCE; COMPETITIVE INHIBITION; CONTROLLED STUDY; DOPAMINE RELEASE; DRUG BINDING SITE; ISOTOPE LABELING; MOLECULAR MODEL; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN CROSS LINKING; PROTEIN ENGINEERING; PROTEIN STRUCTURE; SUBSTANCE ABUSE;

AMINO ACID SUBSTITUTION; ANIMALS; BINDING SITES; BINDING, COMPETITIVE; CERCOPITHECUS AETHIOPS; COCAINE; COS CELLS; DOPAMINE; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; DOPAMINE UPTAKE INHIBITORS; DOSE-RESPONSE RELATIONSHIP, DRUG; MODELS, MOLECULAR; MUTAGENESIS, SITE-DIRECTED; PROTEIN STRUCTURE, TERTIARY; STRUCTURE-ACTIVITY RELATIONSHIP; TIME FACTORS; TRANSFECTION;

EID: 46049086729     PISSN: 10976256     EISSN: None     Source Type: Journal    
DOI: 10.1038/nn.2146     Document Type: Article

References (47)

1. Aguayo, L.G. et al. Historical and current perspectives of neuroactive compounds derived from Latin America. Mini Rev. Med. Chem. 6, 997-1008 (2006).
2. Nnadi, C.U., Mimiko, O.A., McCurtis, H.L. & Cadet, J.L. Neuropsychiatric effects of cocaine use disorders. J. Natl. Med. Assoc. 97, 1504-1515 (2005).
3. Ritz, M.C., Lamb, R.J., Goldberg, S.R. & Kuhar, M.J. Cocaine receptors on dopamine transporters are related to self- administration of cocaine. Science 237, 1219-1223 (1987).
4. Giros, B., Jaber, M., Jones, S.R., Wightman, R.M. & Caron, M.G. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379, 606-612 (1996).
5. Chen, R. et al. Abolished cocaine reward in mice with a cocaine-insensitive dopamine transporter. Proc. Natl. Acad. Sci. USA 103, 9333-9338 (2006).
6. Torres, G.E. & Amara, S.G. Glutamate and monoamine transporters: new visions of form and function. Curr. Opin. Neurobiol. 17, 304-312 (2007).
7. Gether, U., Andersen, P.H., Larsson, O.M. & Schousboe, A. Neurotransmitter transporters: molecular function of important drug targets. Trends Pharmacol. Sci. 27, 375-383 (2006).
8. Iversen, L. Neurotransmitter transporters and their impact on the development of psychopharmacology. Br. J. Pharmacol. 147 Suppl 1: S82-S88 (2006).
9. Chen, N.H., Reith, M.E. & Quick, M.W. Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6. Pflugers Arch. 447, 519-531 (2004).
10. + symporters (NSS) aids in the use of the LeuT structure to probe NSS structure and function. Mol. Pharmacol. 70, 1630-1642 (2006).
11. Zomot, E. et al. Mechanism of chloride interaction with neurotransmitter:sodium symporters. Nature 449, 726-730 (2007).
12. --dependent neurotransmitter transporters. Nature 437, 215-223 (2005).
13. Zhou, Z. et al. LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake. Science 317, 1390-1393 (2007).
14. Singh, S.K., Yamashita, A. & Gouaux, E. Antidepressant binding site in a bacterial homologue of neurotransmitter transporters. Nature 448, 952-956 (2007).
15. Uhl, G.R. & Lin, Z. The top 20 dopamine transporter mutants: structure-function relationships and cocaine actions. Eur. J. Pharmacol. 479, 71-82 (2003).
16. Volz, T.J. & Schenk, J.O. A comprehensive atlas of the topography of functional groups of the dopamine transporter. Synapse 58, 72-94 (2005).
17. Vaughan, R.A. et al. Localization of cocaine analog [125I]RTI 82 irreversible binding to transmembrane domain 6 of the dopamine transporter. J. Biol. Chem. 282, 8915-8925 (2007).
18. Niv, M.Y. & Weinstein, H. A flexible docking procedure for the exploration of peptide binding selectivity to known structures and homology models of PDZ domains. J. Am. Chem. Soc. 127, 14072-14079 (2005).
19. Carroll, F.I., Lewin, A.H., Boja, J.W. & Kuhar, M.J. Cocaine receptor: biochemical characterization and structure-activity relationships of cocaine analogues at the dopamine transporter. J. Med. Chem. 35, 969-981 (1992).
20. Huang, X. & Zhan, C.G. How dopamine transporter interacts with dopamine: insights from molecular modeling and simulation. Biophys. J. 93, 3627-3639 (2007).
21. Kitayama, S. et al. Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding. Proc. Natl. Acad. Sci. USA 89, 7782-7785 (1992).
22. Ukairo, O.T. et al. Recognition of benztropine by the dopamine transporter (DAT) differs from that of the classical dopamine uptake inhibitors cocaine, methylphenidate, and mazindol as a function of a DAT transmembrane 1 aspartic acid residue. J. Pharmacol. Exp. Ther. 314, 575-583 (2005).
23. Lin, Z., Wang, W., Kopajtic, T., Revay, R.S. & Uhl, G.R. Dopamine transporter: transmembrane phenylalanine mutations can selectively influence dopamine uptake and cocaine analog recognition. Mol. Pharmacol. 56, 434-447 (1999).
24. Lee, S.H. et al. Importance of valine at position 152 for the substrate transport and 2β-carbomethoxy-3β-(4-fluorophenyl)tropane binding of dopamine transporter. Mol. Pharmacol. 57, 883-889 (2000).
25. Henry, L.K. et al. Tyr-95 and Ile-172 in transmembrane segments 1 and 3 of human serotonin transporters interact to establish high-affinity recognition of antidepressants. J. Biol. Chem. 281, 2012-2023 (2006).
26. Chen, J.G., Sachpatzidis, A. & Rudnick, G. The third transmembrane domain of the serotonin transporter contains residues associated with substrate and cocaine binding. J. Biol. Chem. 272, 28321-28327 (1997).
27. Bismuth, Y., Kavanaugh, M.P. & Kanner, B.I. Tyrosine 140 of the gamma-aminobutyric acid transporter GAT-1 plays a critical role in neurotransmitter recognition. J. Biol. Chem. 272, 16096-16102 (1997).
28. Henry, L.K., Adkins, E.M., Han, Q. & Blakely, R.D. Serotonin and cocaine-sensitive inactivation of human serotonin transporters by methanethiosulfonates targeted to transmembrane Domain I. J. Biol. Chem. 278, 37052-37063 (2003).
29. Zhou, Y., Bennett, E.R. & Kanner, B.I. The aqueous accessibility in the external half of transmembrane domain I of the GABA transporter GAT-1 Is modulated by its ligands. J. Biol. Chem. 279, 13800-13808 (2004).
30. 2+-binding site. J. Biol. Chem. 274, 36928-36934 (1999).
31. Schwartz, T.W., Frimurer, T.M., Holst, B., Rosenkilde, M.M. & Elling, C.E. Molecular mechanism of 7TM receptor activation - a global toggle switch model. Annu. Rev. Pharmacol. Toxicol. 46, 481-519 (2006).
32. White, K.J., Kiser, P.D., Nichols, D.E. & Barker, E.L. Engineered zinc-binding sites confirm proximity and orientation of transmembrane helices I and III in the human serotonin transporter. Protein Sci. 15, 2411-2422 (2006).
33. Loland, C.J., Granas, C., Javitch, J.A. & Gether, U. Identification of intracellular residues in the dopamine transporter critical for regulation of transporter conformation and cocaine binding. J. Biol. Chem. 279, 3228-3238 (2004).
34. Zomot, E., Zhou, Y. & Kanner, B.I. Proximity of transmembrane domains 1 and 3 of the GABA transporter GAT-1 inferred from paired cysteine mutagenesis. J. Biol. Chem. 280, 25512-25516 (2005).
35. Newman, A.H. & Kulkarni, S. Probes for the dopamine transporter: new leads toward a cocaine-abuse therapeutic - a focus on analogues of benztropine and rimcazole. Med. Res. Rev. 22, 429-464 (2002).
36. Desai, R.I., Kopajtic, T.A., Koffarnus, M., Newman, A.H. & Katz, J.L. Identification of a dopamine transporter ligand that blocks the stimulant effects of cocaine. J. Neurosci. 25, 1889-1893 (2005).
37. Loland, C.J. et al. Relationship between conformational changes in the dopamine transporter and cocaine-like subjective effects of uptake inhibitors. Mol. Pharmacol. 73, 813-823 (2008).
38. Lin, Z. & Uhl, G.R. Dopamine transporter mutants with cocaine resistance and normal dopamine uptake provide targets for cocaine antagonism. Mol. Pharmacol. 61, 885-891 (2002).
39. Chen, R., Han, D.D. & Gu, H.H. A triple mutation in the second transmembrane domain of mouse dopamine transporter markedly decreases sensitivity to cocaine and methylphenidate. J. Neurochem. 94, 352-359 (2005).
40. Sen, N., Shi, L., Beuming, T., Weinstein, H. & Javitch, J.A. A pincer-like configuration of TM2 in the human dopamine transporter is responsible for indirect effects on cocaine binding. Neuropharmacology 49, 780-790 (2005).
41. 2+ switch in the dopamine transporter: mutation of an intracellular tyrosine constitutively alters the conformational equilibrium of the transport cycle. Proc. Natl. Acad. Sci. USA 99, 1683-1688 (2002).
42. Barker, E.L., Moore, K.R., Rakhshan, F. & Blakely, R.D. Transmembrane domain I contributes to the permeation pathway for serotonin and ions in the serotonin transporter. J. Neurosci. 19, 4705-4717 (1999).
43. Ravna, A.W., Sylte, I. & Dahl, S.G. Molecular model of the neural dopamine transporter. J. Comput. Aided Mol. Des. 17, 367-382 (2003).
44. Edvardsen, O. & Dahl, S.G. A putative model of the dopamine transporter. Brain Res. Mol. Brain Res. 27, 265-274 (1994).
45. Katz, J.L., Kopajtic, T.A., Agoston, G.E. & Newman, A.H. Effects of N-substituted analogues of benztropine: diminished cocaine-like effects in dopamine transporter ligands. J. Pharmacol. Exp. Ther. 309, 650-660 (2004).
46. Brooks, B.R. et al. CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 4, 187-217 (1983).
47. Bayly, C.I., Ceplak, P.D., C.W., & Kollman, P.A. A well-behaved electrostatic potential-based method using charge restraints for deriving atomic charges: the RESP model. J. Phys. Chem. 97, 10269-10280 (1993).