The present presentation will give a short overview of G-protein coupled receptors (GPCRs). In mammalian species, there are three main families of GPCRs. Many drug targets belong to family A of GPCRs, which includes receptors for endogenous compounds including biogenic amines, lipid-like compounds, many neuropeptides, glycoprotein hormones, protease-activated receptors and receptors for exogenous compounds, opsins, odorants and some tastants (Kristiansen, 2004). Homology models of GPCRs were previously constructed by using bacteriorhodopsin x-ray structure (not a G-protein coupled receptor) or a template for family A receptor based on a cryo-microscopy microscopy and sequence analysis of family A receptors (Baldwin, 1997). Today, x-ray structures of several family A receptors have been reported, including bovine rhodopsin (Palczewski et al. 2000), beta1(Warne et al., 2008)  and beta2 (Cherezov et al. 2007) adrenergic receptors and A2A adenosine receptor, which has given the opportunity to generate more accurate GPCR models. The x-ray structure of the aminoterminal extracellular domain of family C receptors has also been reported. However, all known x-ray structures of family A receptors represent the inactive state conformation. In the present presentation, a model of the human D2 dopamine receptor constructed by homology with bovine rhodopsin will be discussed. Several antipsychotic drugs were docked into the model by using automatic docking with the modeling software ICM.

Acknowledgements

This study was partly supported by a grant PNRF-103-AI-1/07 from the Norwegian – Polish Research Fund.

References

Baldwin JM, Schertler GF, Unger VM (1997) J Mol Biol. 272:144-64.

Palczewski K et al. (2000) Science 289:739-45.

Kristiansen K (2004) Pharmacol Ther. 103:21-80.

Cherezov Vet al. (2007) Science 318:1258-65

Warne T et al. (2008) Nature 454:486-91.

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