Reviews & Analysis

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.

Assigning function to uncharacterized enzymes discovered through genome projects has provided a great challenge to the fields of informatics, enzymology and structural biology. Docking potential ligands into flexible models of protein structures and docking potential high-energy intermediates, rather than substrates, into known structures are two new computational approaches that have provided a much-needed boost to the field.

The physiological significance of thiaminase II has escaped our understanding for many years. The recent discovery of a new thiamine salvage pathway shows that this enzyme is involved in the regeneration of precursors for thiamine biosynthesis.

Chemical probes reveal Hsp90 to be a key molecule for the control of apoptosis in small-cell lung cancer—with important implications for Hsp90 biology and cancer treatment.