Reviews & Analysis

Subterranean termite colonies are founded by a single king and queen. However, the king generally outlives the queen, and an optimal number of secondary termite queens must be produced to meet the reproductive needs of the colony. A recent study explains the chemical basis of this biological process.

Selectivity is a key obstacle in drug development. A new study describes how “peptide stapling,” a technique for making peptide α-helices more potent and cell permeable, allows the design of MCL-1 inhibitors with extraordinary selectivity.

Siderocalin (also known as lipocalin 2) is a component of the innate immune system that binds and sequesters bacterial iron compounds in the blood and urine. A new study identifies iron–catechol complexes as endogenous ligands for siderocalin, which can deliver the iron compounds to the kidney.

Time-resolved fluorescence resonance energy transfer (TR-FRET) measurements with selective, fluorescently labeled ligands support the existence of GPCR dimers in native tissues and suggest that activated GPCR dimers are asymmetric.

Protein structures are considerably stabilized by local interactions. A new computational and structural analysis discovers that n→π^* interactions between consecutive residues are stabilizing and ubiquitous in a variety of secondary structures.

TAP is an ABC transporter that contributes to antigen presentation by transporting peptides from the cytosol to the ER lumen for loading onto MHC-I. Viral evaders of the host immune system take advantage of TAP’s structure as well as its ATP-binding ability and have provided new insight into its function.

The susceptibility of organisms to chemical perturbation differs as a result of defenses that limit the permeation of small molecules. Screening for permeation, rather than bioactivity, to identify a priori organism-specific chemical space offers an intriguing approach to phenotypic assays and potentially addresses some fundamental challenges in drug discovery.

Epistatic maps are used to delineate the modes of interaction of genes in various cellular pathways. A new epistatic map of nearly 400 genes involved in plasma membrane biology has revealed unexpected modes of regulation of endocytosis and sphingolipid metabolism.

The kinetics of the acylation, deacylation and reacylation cycle are important for localization and function of Ras as well as other key signaling proteins. A new small-molecule inhibitor may put the brakes on Ras by inhibiting the deacylation enzyme APT1.

Systems biology methods accumulate a vast array of information to generate hypotheses and discover new cellular relationships. A combination of 'omics' technologies now provides important proof of biochemical predictions and creates new opportunities for understanding cellular functional architecture.

A new study fulfills a central goal of post-genomic medicine, the treatment of inherited loss-of-function disorders not by correcting a genetic mutation but by augmenting the efficiency with which the nascent mutant gene product undergoes conformational maturation and is deployed to its site of action.

Bacterial polysaccharides exhibit remarkable structural diversity and play critical roles in the biology of their producing organisms. A recent study defines the minimal machinery for polymerization in a widely disseminated assembly pathway.

The ability to degrade atrazine has been engineered in a strain of Escherichia coli capable of responding specifically to the presence of the herbicide. A chemical biology approach generated an atrazine-sensitive riboswitch enabling a cellular response to occur only in the presence of the toxin.

Drugs identified in high-content screens are often difficult to link to the cellular target, especially when multiple signaling pathways impinge on the phenotypic endpoint. A chemical-genetic approach in fruit fly cells now greatly improves the prioritization of drug hits by directing the screen toward a single pathway.

COX-2 is the enzyme largely responsible for causing inflammation, a common mechanism of disease. A study now reports that derivatives generated by COX-2 from naturally occurring ω-3 fatty acids are anti-inflammatory mediators.

Bacteria resistant to glycopeptides such as vancomycin sense the drugs and escape killing by remodeling synthesis of the cell wall target. A photoaffinity probe shows that induction of resistance relies on direct drug recognition by a glycopeptide sensor.

Functionally coupled motions between the voltage-sensing and the phosphatidylinositol phosphatase domains of the sea squirt protein Ci-VSP is mediated by PI(4,5)P₂ binding to the intervening linker, shedding light on the function of an unusual voltage-sensing protein.