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Volume 4 Issue 2, February 2008

Quantitative flow cytometric measurement of protein phosphorylation has been developed into a high-throughput drug screening platform that can be used throughout the drug discovery process. Using phosphoflow cytometry, Krutzik et al. (p 132) studied the effects of compounds from a natural product library on cytokine-induced phosphorylation of multiple proteins in the Jak-Stat signaling pathway in subpopulations of primary immune cells. Shown are several Tetris-inspired (http://www.tetris.com) game pieces depicting library compounds, flow cytometric histograms and scatter plots, dose-response curves, and the structure of the Stat1 protein, together forming a heatmap representation of the screening data and revealing pathway- and cell type-specific inhibitors. Cover art by Erin Boyle based on images provided by Peter O. Krutzik and Garry P. Nolan.

Volume 4 Issue 2

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Editorial

  • The pharmaceutical industry faces major challenges in delivering the next generation of therapeutic agents. The shared interests of pharmaceutical researchers and chemical biologists provide impetus for new drug discovery innovations.

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News & Views

  • Recent crystal structures of a bacterial copper tolerance protein reveal an intriguing copper binding site that includes tryptophan. Its close proximity coupled with spectroscopic data suggests an unusual cation-π interaction between Cu(I) and the aromatic ring of tryptophan.

    • Katherine J Franz
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  • The MRN protein megacomplex mediates repair of double-stranded DNA breaks (DSBs) by tethering together broken ends of chromosomes and signaling a cascade of events required for DNA repair. The first small-molecule inhibitor that disrupts MRN function provides a valuable new tool for functional studies of DSB repair in cells.

    • James T Stivers
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  • Extending the time animals spend in the vigorous phase of their lives would have enormous economical and social consequences. A new study reveals that antidepressants commonly used in humans can significantly prolong the life of nematodes by antagonizing conserved G protein–coupled receptors.

    • Peter John Roy
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  • Myristoylation is an important post-translational modification that targets many signaling proteins to membranes. Now the crystal structure of calcium-bound myristoylated GCAP-1 demonstrates a new structural role for protein myristoylation.

    • Lee P Haynes
    • Robert D Burgoyne
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  • Schizophrenia is thought to involve a dysfunction of glutamatergic and GABAergic signaling in the prefrontal cortex, but how these systems interact in the disease has been unclear. Now ketamine, a glutamatergic NMDA receptor antagonist, may provide a mechanism that could link these pathways.

    • Jeremy Seamans
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