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Pharmacological and genetic modulators of voltage-gated Ca2+ channel (CaV) activity have been useful tools for understanding and modulating excitable cell function. A new method combines these approaches to provide pharmacological control of a genetically encoded suppressor of CaV activity.
Multimodular scaffold proteins are ideally suited for assembling the various proteins in signaling pathways into supramolecular complexes. A recent study demonstrates that, in addition to a passive scaffolding role, a PDZ domain in a photoreceptor scaffold protein actively regulates fruit fly visual signaling via light-dependent conformational cycling.
DNA is the newest member of the enzyme club. The first glimpse of DNAzyme conformational changes at the single-molecule level reveals that enzymes made of DNA can use the same modi operandi as protein and RNA catalysts.
Nitric oxide–mediated production of cyclic guanosine 3′,5′-monophosphate (cGMP) is a crucial signal transduction pathway that controls a wide array of biological functions. A new layer of complexity in mammalian cell regulation is revealed by the discovery of a redox-active nitrated cGMP derivative with the ability to post-translationally modify protein thiol residues by S-guanylation.
A phosphorothioate modification of DNA has been identified in bacteria. This first observed alteration of the DNA phosphate backbone opens many questions about the mechanism of sulfur incorporation and the function of this modification.
A recently characterized 'M-box' genetic switch from bacteria is proposed to directly sense cellular Mg2+ levels through the conformation of its newly synthesized RNA. This Mg2+-sensing riboswitch controls transcription termination in front of a Mg2+ transporter gene, thus introducing a new and direct level of genetic regulation to metal ion homeostasis.
The C12 'earthy' odorant geosmin is derived from the C15 metabolite farnesyl diphosphate. Metabolic transformation now seems to be catalyzed by a bifunctional protein having two operatively independent sesquiterpene synthase domains. The domains are catalytically linked through the passive diffusion of a C15 alcohol product of the N-terminal catalytic domain to the C-terminal catalytic domain for the final steps of geosmin formation.
An emerging view is that high-fidelity metal selection by the proteins involved in metal homeostasis is pivotal to ensure that the correct metals bind to nascent metalloproteins. A new study demonstrates that the AztA zinc exporter performs this function by using tandem metal-binding domains to entrap some of the wrong metals in nonproductive complexes.
A fully synthetic three-component vaccine has been shown to induce high titers of antibodies against the mucin Tn antigen of human cancer cells. The vaccine's superior properties are a result of the covalent incorporation of a ligand for Toll-like receptors and the presentation of the vaccine in a liposome format.
Monitoring nutritional sufficiency is essential in optimizing bacterial survival strategies. Recent studies find that nutrient sensing is delocalized over many cell components. Adding to the complexity, some metabolite pools and cellular components contribute to more than one signal transduction pathway and to housekeeping functions.
Transmembrane electrochemical ion gradients are the thermodynamic forces exploited by living cells to drive specific substances across the membrane. A new study begins to reveal the molecular mechanisms by which a transporter protein harnesses these driving forces.
The use of biocatalysts for glycoside bond formation is an attractive strategy in chemical synthesis, but the tight specificity of enzymes can be a significant limitation. An ingenious screening strategy has led to the discovery of a particularly plastic glycosyltransferase.
Heterologous production of natural products in non-native bacteria can be used to increase yields of certain bioactive compounds; however, producing small molecules inside bacteria has numerous limitations. Two reports of the in vitro reconstruction of entire biosynthetic pathways highlight the advantages and challenges of this approach for pathway engineering.
The U2 snRNP particle is an essential component of the eukaryotic pre-mRNA splicing apparatus, the spliceosome. Natural and semisynthetic inhibitors that bind the SF3b subunit of the U2 snRNP block splicing and prompt nuclear export of intron-bearing precursors, defining a new mode of action in anticancer drugs.
Bacterial mRNAs begin with a triphosphate on the first transcribed nucleotide, but RNase E, the endonuclease long thought to initiate mRNA decay in Escherichia coli, only works well on RNA with a 5′-monophosphate. Conversion of the 5′-triphosphate to a monophosphate now appears to be the first committed step in mRNA decay in E. coli.
Organomercurial lyase (MerB) catalyzes the difficult cleavage of C-Hg bonds to hydrocarbon and mercuric dithiol products. Model compounds providing two or three thiolate ligands activate organomercurials toward acidic cleavage under mild conditions, which supports a mechanism in which MerB enzymes use two conserved active-site cysteines to activate the substrate.
