Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Volume 5 Issue 7, July 2009

An inhibitor 'hijacks' kinase regulation. Okuzumi et al. (p 484) investigated the mechanism by which the ATP-competitive Akt inhibitor A-443654 induces hyperphosphorylation of Akt regulatory sites. Using chemical genetic tools, the authors found that inhibitor binding, rather than pathway feedback, directly triggers Akt hyperphosphorylation (see also News and Views by Frye and Johnson on p 448). The cover shows Akt in contact with two regulatory kinases, PDK and mTORC2, and an analog of A-443654. Cover art by Erin Dewalt.

Volume 5 Issue 7

Subscribe

Editorial

  • Identifying and increasing access to the highest quality chemical probes will ensure their prominent position in the biological and drug discovery toolboxes.

    Editorial

    Advertisement

Top of page ⤴

Commentary

Top of page ⤴

News & Views

  • Small-molecule inhibitors can induce phosphorylation priming of AGC kinases. Priming by ATP binding pocket conformation, rather than intrinsic kinase activity, has significant implications for drug discovery and therapeutic efficacy.

    • Stephen V Frye
    • Gary L Johnson
    News & Views

  • Microorganisms are a major source of new therapeutics. However, the discovery and sustainable production of these compounds are often hampered owing to limited access to biosynthetic genes or products. Recent studies provide new approaches for targeting biosynthesis genes in the metagenome of complex microbial assemblages and for inducing the expression of otherwise silent biosynthesis genes.

    • Christian Hertweck
    News & Views

  • A new methodology combining small molecules and phage-displayed peptides enables the isolation of chemically modified bicyclic peptides capable of high-affinity recognition of target proteins.

    • Dario Neri
    • André W Brändli
    News & Views

  • Westheimer's classical proposal that the decreased pKa of Lys115 in the active site of acetoacetate decarboxylase is the result of its unfavorable electrostatic juxtaposition with Lys116 has been evaluated by X-ray crystallography. The long-awaited structure reveals that Lys115 is positioned in a hydrophobic pocket that lowers its pKa.

    • John A Gerlt
    News & Views
Top of page ⤴

Brief Communication

Top of page ⤴

Article

Top of page ⤴

In This Issue

Top of page ⤴

Search

Advanced search

Quick links