Reviews & Analysis

Near-field scanning optical microscopy has been used to study the organization of β₁- and β₂-adrenergic receptors in cardiac cells. The fluorescently labeled receptors organize into distinct clusters, which may represent localization in microdomains such as lipid rafts and caveolae.

Activity-based probes can be used for monitoring enzyme activity based on their covalent reactions with active-site residues. A quenched activity-based probe has now been developed that becomes fluorescent only after labeling active proteases. The specificity of the fluorescent signal and cell permeability of the small molecule make this probe effective for monitoring protease activity in living cells.

Protein nitrosation is an important signaling mechanism in vivo; however, mechanisms for selective nitric oxide modification of cysteines have not been described. Thioredoxin is now shown to rapidly and site-specifically catalyze S-nitrosation of an active site cysteine of caspase-3.

The identification of promising lead compounds from high-throughput screens is still a very complex problem. A new high-throughput assay for identifying aggregation-based false positives could help.

In the competition for control of iron between Mycobacterium tuberculosis and host cells, very little is understood about how these bacteria use small-molecule siderophores to obtain iron. A mechanism is now shown for intracellular iron acquisition by mycobacterial lipophilic siderophores.

Apoptosis occurs through precise cellular pathways, whereas necrosis is generally thought of as a nonspecific cellular response to external damage. However, identification of a chemical inhibitor of necrotic events suggests that specific molecular pathways can also trigger necrosis.

Retroviruses have a stretch of RNA that dimerizes during viral particle formation. A new study suggests that RNA flexibility in the monomeric form may facilitate dimerization or other RNA-dependent viral functions.

Prenylation represents a critical step in the biosynthesis of many natural products. A new study reveals how aromatic prenyltransferase enzymes tolerate diverse aromatic polyketides while still controlling the length of prenyl side chains.

Identification of endogenous glycan-binding ligands for cell-surface receptors has been difficult. Incorporation of a photoactive sialic acid analog into B-cell surface glycoproteins suggests that CD22 molecules may cluster by binding carbohydrate antigens on neighboring CD22 molecules.

Ribozymes are enzymes comprised of RNA that fold into three-dimensional structures and that catalyze chemical reactions central to all cells. A new study shows that ribozymes, like proteins, may use general acid catalysis as part of their catalytic toolkit.

ComX is a post-translationally modified peptide involved in quorum sensing in Bacillus subtilis. The structure of ComX has now been shown to contain a geranylated tryptophan with an unusual tricyclic architecture.

Nitric oxide signaling requires that the heme of soluble guanylate cyclase bind NO preferentially to O₂. Engineering of the enzyme's active site reveals a molecular basis for NO binding selectivity.

The fate of cells depends on a delicate balance of pro- and anti-apoptotic proteins. Small-molecule inhibitors of anti-apoptotic protein-protein interactions promote apoptosis in cancer cells.