A competitive inhibitor traps LeuT in an open-to-out conformation

Science

Volumn 322, Issue 5908, 2008, Pages 1655-1661

  Singh, Satinder K ^a   Piscitelli, Chayne L ^a   Yamashita, Atsuko ^b,c   Gouaux, Eric ^a  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b Och Spine at New York Presbyterian Hospitals   (United States)

^c RIKEN SPring 8 Center ^*  (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; ASPARTIC ACID; LEUCINE; MEMBRANE PROTEIN; SEROTONIN TRANSPORTER; TRYPTOPHAN;

CATALYSIS; CRYSTALLOGRAPHY; CYTOLOGY; INHIBITION; INHIBITOR; MEMBRANE;

ARTICLE; CELL MEMBRANE; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; KINETICS; NEUROTRANSMISSION; PRIORITY JOURNAL;

AMINO ACID TRANSPORT SYSTEMS; AMINO ACIDS; BACTERIAL PROTEINS; BINDING SITES; BINDING, COMPETITIVE; BIOLOGICAL TRANSPORT; CRYSTALLIZATION; CRYSTALLOGRAPHY, X-RAY; HYDROGEN BONDING; HYDROPHOBICITY; KINETICS; LEUCINE; LIGANDS; MODELS, BIOLOGICAL; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; SODIUM; SYMPORTERS; TRYPTOPHAN;

EID: 58149233796     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1166777     Document Type: Article

References (39)

1. S. M. Parsons, FASEB J. 14, 2423 (2000).
2. M. J. Roux, S. Supplisson, Neuron 25, 373 (2000).
3. N. Zerangue, M. P. Kavanaugh, Nature 383, 634 (1996).
4. N. H. Chen, M. E. Reith, M. W. Quick, Pflugers Arch. 447, 519 (2004).
5. B. I. Kanner, J. Membr. Biol. 213, 89 (2006).
6. U. Warskulat, A. Reinen, S. Grether-Beck, J. Krutmann, D. Haussinger, J. Invest. Dermatol. 123, 516 (2004).
7. J. Masson, C. Sagne, M. Hamon, S. E. Mestikawy, Pharmacol. Rev. 51, 439 (1999).
8. M. K. Hahn, R. D. Blakely, Pharmacogenomics J. 2, 217 (2002).
9. N. Ozaki et al., Mol. Psychiatry 8, 933 (2003).
10. G. B. Richerson, Y. Wu, Adv. Exp. Med. Biol. 548, 76 (2004).
11. J. S. Sutcliffe et al., Am. J. Hum. Genet. 77, 265 (2005).
12. J. R. Shannon et al., J. Med. 342, 541 (2000).
13. G. S. Salomons et al., Am. J. Hum. Genet. 68, 1497 (2001).
14. B. Heller-Stilb et al., FASEB J. 16, 231 (2002).
15. E. L. Barker, R. D. Blakely, in Psychopharmacology: the Fourth Generation of Progress, F. E. Bloom, D. J. Kupfer, Eds. (Raven Press, New York, 2000), pp. 321-333.
16. P. Krogsgaard-Larsen, B. Frolund, K. Frydenvang, Curr. Pharm. Des. 6, 1193 (2000).
17. S. G. Amara, M. S. Sonders, Drug Alcohol Depend. 51, 87 (1998).
18. A. Yamashita, S. K. Singh, T. Kawate, Y. Jin, E. Gouaux, Nature 437, 215 (2005).
19. S. K. Singh, A. Yamashita, E. Gouaux, Nature 448, 952 (2007).
20. Z. Zhou et al., Science 317, 1390 (2007).
21. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
22. J. Talvenheimo, P. J. Nelson, G. Rudnick, J. Biol. Chem. 254, 4631 (1979).
23. S. Apparsundaram, D. J. Stockdale, R. A. Henningsen, M. E. Milla, R. S. Martin, J. Pharmacol. Exp. Ther. 327, 982 (2008).
24. H. K. Kimelberg, E. W. Pelton 2nd, J. Neurochem. 40, 1265 (1983).
25. L. K. Henry et al., J. Biol. Chem. 281, 2012 (2006).
26. S. Faham et al., Science 321, 810 (2008).
27. Materials and methods are available as supporting material on Science Online.
28. L. Celik, B. Schiott, E. Tajkhorshid, Biophys. J. 94, 1600 (2008).
29. L. Shi, M. Quick, Y. Zhao, H. Weinstein, J. A. Javitch, Mol. Cell 30, 667 (2008).
30. L. R. Forrest et al., Proc. Natl. Acad. Sci. U.S.A. 105, 10338 (2008).
31. Y. Zhou, E. R. Bennett, B. I. Kanner, J. Biol. Chem. 279, 13800 (2004).
32. A. Rosenberg, B. I. Kanner, J. Biol. Chem. 283, 14376 (2008).
33. L. K. Henry, E. M. Adkins, Q. Han, R. D. Blakely, J. Biol. Chem. 278, 37052 (2003).
34. B. A. Hirayama, A. Diez-Sampedro, E. M. Wright, Br. J. Pharmacol. 134, 484 (2001).
35. A. Androutsellis-Theotokis et al., J. Biol. Chem. 278, 12703 (2003).
36. T. Beuming, L. Shi, J. A. Javitch, H. Weinstein, Mol. Pharmacol. 70, 1630 (2006).
37. S. Weyand et al., Science 322, 709 (2008).
38. J. Tsai, R. Taylor, C. Chothia, M. Gerstein, J. Mol. Biol. 290, 253 (1999).
39. We are grateful to the staff of National Synchrotron Light Source beamline X29A and Advanced Light Source beamlines 8.2.1 and 8.2.2 for assistance with data collection. S.K.S. was supported by an individual NIH/National Institute of Neurological Disorders and Stroke National Research Service Award postdoctoral fellowship and a NIH/National Institute of Mental Health K99/R00 Pathway to Independence Award. C.L.P. was supported by an institutional NIH Multidisciplinary Training in Neuroendocrinology grant. A.Y. was on leave from the Laboratory for Structural Biochemistry, RIKEN Harima Institute at SPring-8, Japan. This work was supported by NIH (E.G.). E.G. is an investigator with the Howard Hughes Medical Institute. Coordinates and structure factors of the LeuT complexes have been deposited in the Protein Data Bank with the following accession codes: glycine (3F4J), alanine (3F48), 30 mM Leu (3F3E), methionine (3F3D), selenomethionine (3F4I), 4-fluorophenylalanine (3F3C) and Trp (3F3A).