PHARMACOLOGY From in Silico to in Vitro Drug Discovery

Many currently available therapeutic drugs act by modulating signaling through G protein (heterotrimeric GTP-binding protein)-coupled receptors. The G protein ß subunit transmits signals from G protein-coupled receptors to target proteins, and many crystal structures of such complexes have been solved. Bonacci et al. (see the Perspective by Tesmer) used a computer program to predict which chemical compounds would bind to the interaction site on the ß subunits and obtained potent small-molecule inhibitors of protein-protein interactions. Furthermore, these molecules showed specificity for disrupting signaling-specific downstream targets, which suggests that such reagents might be both effective and relatively free of side effects.

T. M. Bonacci, J. L. Mathews, C. Yuan, D. M. Lehmann, S. Malik, D. Wu, J. L. Font, J. M. Bidlack, A. V. Smrcka, Differential targeting of Gß-subunit signaling with small molecules. Science 312, 443-446 (2006). [Abstract] [Full Text]

J. J. G. Tesmer, Hitting the hot spots of cell signaling cascades. Science 312, 377-378 (2006). [Summary] [Full Text]

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In Science Signaling

REVIEWS
G Protein Signaling: Insights from New Structures

Anita M. Preininger and Heidi E. Hamm (3 February 2004)
Sci. STKE 2004 (218), re3. [DOI: 10.1126/stke.2182004re3]
 |  Gloss »  |  Abstract »  |  Full Text »  |  PDF »  |  Animation »  |  Structure Movie »  |  Erratum and Update »

PROTOCOLS
G COOH-Terminal Minigene Vectors Dissect Heterotrimeric G Protein Signaling

Annette Gilchrist, Anli Li, and Heidi E Hamm (5 February 2002)
Sci. STKE 2002 (118), pl1. [DOI: 10.1126/stke.2002.118.pl1]
 |  Abstract »  |  Full Text »  |  PDF »