Reviews & Analysis

Aerobic inactivation of hydrogenases is a serious limitation to applications of the enzyme in biotechnology and has been extensively studied. A recent investigation combining electrochemical and spectroscopic methods shows that the molecular species that form as a result of exposure to O₂ can be formed anaerobically and thus cannot involve incorporation of oxygen in the enzyme.

Conformational targeting enabled the creation of a ubiquitin variant that specifically inhibits the deubiquitinating enzyme ubiquitin-specific protease 7 (also known as HAUSP). Generation of such tools is essential to unravel the complexities of ubiquitin signaling, but how general is this approach?

New, bioactive marine sponge compounds that function as inhibitors of the poly (ADP-ribose) polymerase family of proteins have now been identified to promote the correction of cystic fibrosis. Poly (ADP-ribose) polymerase inhibitors may be managers of proteostasis biology, consistent with their role (or roles) in remediation of inflammatory states.

A major determinant of the ion flux rate through acetylcholine receptors is a ring of five residues, four glutamates and a glutamine, at the channel's cytoplasmic mouth. The glutamates adopt alternate rotamer conformations so that only two directly affect channel conductance.

Combinatorial protein engineering based on structural data and the differential expression of alternate second receptor chains for interleukin-4 (IL-4) is used to modify and tune cellular specificity on primary human cells.

Post-translational modification of proteins by N-acetylglucosamine (O-GlcNAc) is carried out by a single glycosyltransferase, OGT. Two independent groups have generated structures of ternary complexes that elegantly illuminate substrate and product binding modes, and thus the overall reaction coordinate, but the respective authors differ in their choice of catalytic base.

A gain of function in the cancer-associated mutant of isocitrate dehydrogenase inspired protein engineering of Saccharomyces cerevisiae homoisocitrate dehydrogenase to create a 2-hydroxyadipate dehydrogenase. This neoactivity yields chirally pure (R)-2-hydroxyadipic acid, a synthetic precursor to the industrially valuable adipic acid used in pharmaceuticals and synthetic polymers.

The first direct chemical inhibitor of a key histone-methylating enzyme provides a new tool to alter epigenetic states and genome expression profiles in normal and cancer cells.

A metabolic route including a RubisCO-like protein links polyamine metabolism with isoprenoid biosynthesis in the photosynthetic bacterium Rhodospirillum rubrum. Methanethiol is released in the pathway but is recaptured in the form of methionine, and thus methylthioadenosine, previously regarded as something of a byproduct of polyamine biosynthesis, is converted to two major cell components.

Bacterial persisters consist of a phenotypic subpopulation that survives antibiotic treatment, prolonging infection. The GhoT toxin from the newly discovered ghoS-ghoT toxin-antitoxin system contributes to persistence, most likely by interfering with bacterial inner membrane integrity.

The phospholipid-lysophospholipid transacylase tafazzin is responsible for enrichment of the cardiolipin fraction of mitochondria with tetralinoleoyl-cardiolipin. The specificity for linoleoyl hydrocarbon chains is now explained by the specific action of tafazzin on negatively curved lipid monolayers.

By incorporating sequence homology and context associations, global probabilistic approaches to annotate genome-scale metabolic networks can substantially improve the accuracy of biochemical predictions, revealing potential functionality and directing experimental validation.

Single-molecule observations reveal that lipid- and protein-based interactions jointly contribute to the interactions among glycosylphosphatidylinositol-anchored proteins in membranes. Understanding these interactions will help to refine long-evolving (and still debated) models of 'raft' domains in biological membranes.

Glycosyltransferases, enzymes that catalyze glycosidic bond formation, are one of the most important but least well-characterized protein families found in nature. A new label-free, high-throughput glycan array–based strategy enables rapid profiling of tens of thousands of potential glycosyltransferase reactions.

Type IV collagen, a major constituent of basement membranes, contains an unusual intermolecular sulfilimine crosslink whose route of biosynthesis has remained undefined. An oxidative triad consisting of peroxidasin, H₂O₂ and halide is now shown to drive sulfilimine generation in vivo.

Siderophores are small molecules allowing microorganisms to competitively acquire iron from soils, aquatic systems or host proteins. New research shows that a siderophore secreted by some bacterial pathogens also binds copper and protects against host-derived copper toxicity during infection.

Bacterial pili are surface fibers that must resist high shearing forces to remain associated with their target. The Escherichia coli type 1 pilus chaperone FimC serves as a 'sensor', ensuring that only stable pilins become incorporated into the growing fiber.

Dissecting the often subtle or time-sensitive roles of glycans in biology demands an increased availability of high-quality inhibitors for carbohydrate-processing enzymes. A review of lessons learned from other fields and considerations unique to glycobiology provides guidelines for development of these critical chemical tools.

The proapoptotic cysteine protease caspase-6 participates in the neuropathology of several diseases. Unlike the active dimeric form, the caspase-6 zymogen forms a unique tetramer that can be stabilized by allosteric inhibitors, which prevents caspase-6 activation.