Volume 7 Issue 4, April 2011

Amorphous mineral phases play important roles in the skeletons of many organisms, but the molecular basis for species-specific control is still under debate. The demonstration that energy-rich metabolites such as phosphoenolpyruvate stabilize amorphous calcium carbonate (ACC) in crayfish inspires speculation about calcium minerals in emerging metabolisms.

Detailed biophysical and biochemical studies provide an exquisite example of how conformational flexibility controls the interaction between an intrinsically disordered protein and its numerous binding partners.

High-throughput screening in Caenorhabditis elegans identified a compound that distinctly regulates fat storage and feeding, highlighting new players in energy homeostasis.

The assembly of chimeric synthetic pathways in cell factories will enable production of novel fuels and chemicals by microbial fermentation. The assembly of five enzymes for production of 1-butanol in Escherichia coli using kinetic considerations provides new lessons regarding these endeavors.

The mechanisms and molecules involved in controlling biomineral formation remain unclear, though several proteins have been implicated in the process. Examination of crayfish now surprisingly points to upregulated glycolytic metabolites as playing a critical role in stabilizing amorphous calcium carbonate.

Assisted by 3,800 chemical bioactivities, a bioinformatic analysis explores the inter-relatedness of over 170 kinases and generates a kinase interaction map based on sequence and ligand-binding activity that challenges the robustness of drug interaction networks.

A potent and selective inhibitor of the kinase LRRK2 identified using an in vitro ATP-site competition binding assay also inhibits the G2019S mutant, implicated in Parkinson's disease, as well as the regulatory feedback loop where LRRK2 is phosphorylated and binds 14-3-3 protein.

A screen for compounds that alter fat content in C. elegans identifies a novel agonist of an AMP-activated kinase pathway that reduces fat storage as well as implicates the transcription factor K08F8.2 as a regulator of fat metabolism.

NMR reveals the dynamic stretching ability of the subdomain LH of the intrinsically disordered p21, providing a physical basis for the binding and functional diversity in its cell cycle regulatory role as a modulator of Cdk–cyclin complexes.

As metabolic reactions are often in equilibrium, product sequestration is often used to drive engineered pathways forward. For n-butanol, however, this is not possible; instead, introducing kinetic barriers for backwards reactions significantly increases product yield.

The use of synthetic analogs to explore substrate promiscuity during trehalose incorporation into the mycobacterial cell wall yields a fluorescent probe that can be used to examine M. tuberculosis cell biology and detect this harmful pathogen within macrophages.

RNase T is a 3′-to-5′ exonuclease involved in RNA maturation pathways. Biochemical and three-dimensional structures of RNase T in complex with single- or double-stranded DNA reveal mechanisms of substrate selection and catalysis by this nuclease.