Editors' ChoiceG Protein–Coupled Receptors

Tweaking Dopamine Reception

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Sci. Signal.  23 Nov 2010:
Vol. 3, Issue 149, pp. ec358
DOI: 10.1126/scisignal.3149ec358

Dopamine modulates many cognitive and emotional functions of the human brain by activating G protein–coupled receptors. Antipsychotic drugs that block two of the receptor subtypes are used to treat schizophrenia but have multiple side effects. Chien et al. (see the Research Article by Wu et al.) resolved the crystal structure of one receptor in complex with a small-molecule inhibitor at 3.15 angstrom resolution. Homology modeling with other receptor subtypes might be a promising route to reveal potential structural differences that can be exploited in the design of selective therapeutic inhibitors having fewer side effects.

E. Y. T. Chien, W. Liu, Q. Zhao, V. Katritch, G. W. Han, M. A. Hanson, L. Shi, A. H. Newman, J. A. Javitch, V. Cherezov, R. C. Stevens, Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 330, 1091–1095 (2010). [Abstract] [Full Text]

B. Wu, E. Y. T. Chien, C. D. Mol, G. Fenalti, W. Liu, V. Katritch, R. Abagyan, A. Brooun, P. Wells, F. C. Bi, D. J. Hamel, P. Kuhn, T. M. Handel, V. Cherezov, R. C. Stevens, Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330, 1066–1071 (2010). [Abstract] [Full Text]