Volume 10 Issue 5, May 2014

Itaconate is a metabolite secreted by activated macrophages that inhibits pathogen growth. Some pathogens use itaconate degradation enzymes to promote their survival and infectivity, highlighting metabolic pathways to be considered in host-pathogen interactions.

Maintenance of the pluripotent stem cell state is regulated by the post-translational modification of histones. The discovery that citrullination of the linker histone H1 is critical to this process represents a new role for the protein arginine deiminases in development.

A bioorthogonal decaging strategy, mediated by small-molecule palladium compounds, can recover the lysine-dependent activity of cellular proteins. This activation technique could be generally applicable for controlling and probing function of a protein target in living cells.

Methane is an energy resource that is currently being wasted through emissions, venting and flaring during petroleum extraction. Recent discoveries regarding the basis of enzyme function and microbial metabolism provide the foundation for new thinking about how to reclaim this resource through bioconversion.

Lasso peptides are antimicrobial bacterial peptides that hijack outer membrane siderophores to kill target cells. The structural and biochemical basis of antimicrobial lasso peptide MccJ25 binding to siderophore FhuA explains why these peptides have a narrow range of target species.

A new small-molecule inhibitor of the Hedgehog signaling pathway acts independently of Smoothened (Smo). Rather than acting through Smo, which is a GPCR-like protein of the pathway, the compound acts through the orphan GPCR GPR39, with the level of GPR39 activation correlating with Hh pathway inhibition.

High-resolution microscopy and biochemistry show that homoclusters of GPI-anchored proteins (GPI-APs) in the Golgi arrive at the apical membrane of polarized cells and then coalesce into larger heteroclusters. Therefore, sorting at the Golgi determines organization of GPI-APs at the plasma membrane.

Biophysical analysis reveals that conserved G-rich sequences within the mRNAs of gammaherpesvirus genome maintenance proteins (GMPs) form G-quadruplexes (G4). Stabilization of mRNA G4 motifs represses GMP translation, whereas destabilization enhances translation, suggesting that these RNA elements are cis-acting translational regulators of proteins involved in viral latency.

Histone post-translational modifications are important regulators of chromatin structure and gene expression. Lysine 2-hydroxisobutyrylation sites, discovered by MS and validated by chemical synthesis, are found in active chromatin and associated with male germ cell differentiation.

Host cells respond to bacterial infection by producing itaconate, an inhibitor of bacterial metabolism, among other strategies. Biochemical characterization now defines genes known to be important for bacterial virulence as a new pathway that degrades itaconate into metabolic building blocks.

Certain oxygen-tolerant hydrogenases contain a unique [4Fe-3S] cluster near the catalytic site, but the role of this cofactor is not fully understood. Crystallographic, spectroscopic and computational data now provide evidence for redox-dependent transformations of this cluster, potentially explaining how specialized hydrogenases can safely reduce inhibitory O₂.

De novo enzyme designs have generally tried to optimize multiple aspects of enzyme function simultaneously. Focusing only on positioning of active site residues to generate a nucleophilic serine as assessed by activity-based protein profiling now leads to a successful intermediate design.

Bioretrosynthesis is meant to simplify construction of metabolic pathways by screening only for the final desired product. This approach, aided by protein design and crystallography, is now used to synthesize an antiretroviral nucleoside analog and surprisingly identifies a new enzyme function.

NMR structural data and biophysical and biological experiments show that the antifungal compound amphotericin is toxic because it acts as a sterol sponge by interacting with ergosterol on the fungal membrane and extracting it from within the membrane to the surface of the membrane.