Volume 15 Issue 12, December 2019

The last step of archaeosine biosynthesis was found to involve two enzymes, the previously known ArcS with lysine transfer activity and a novel identified radical SAM enzyme named RaSEA.

Actin cytoskeletal structures are essential for many cellular processes, and cofilin is a key protein for the assembly of these highly dynamic structures. A new cofilin construct enables precise optogenetic control of actin assembly in live cells.

The regulation of brain iron homeostasis, previously thought to be cell autonomous and modulated by local factors in the interstitial fluid, is reported by Wang et al. to be strongly influenced by axonal transport of iron in an activity-dependent and unidirectional manner between functionally associated regions. The supply of iron from the ventral hippocampus to the middle prefrontal cortex subserved an anxiolytic phenotype and mediated the neuropharmacological actions of diazepam and lithium chloride in rodent models.

This Perspective focuses on the chemical basis of ferroptotic cell death, discussing the prominent role of spontaneous chemical reactions, how they depend on enzyme-catalyzed processes and how to exploit this interplay for therapeutic benefit.

Euryarchaeal ArcS alone cannot produce G⁺-containing tRNA but works as a lysine transferase to produce a lysine adduct intermediate, which finally forms G⁺-containing tRNA in the presence of a newly identified SAM enzyme, RaSEA.

A crystal structure of prokaryotic pentameric ligand-gated ion channel ELIC reveals a lipid-binding site at the interface between subunits that is shaped by a flexible helix important for channel desensitization upon lipid binding.

The combination of multiple fluorophores on a hybridized DNA scaffold enables the development of the reporter cHOClate, which is used to simultaneously and quantitatively image hypochlorous acid (HOCl) and pH during phagosome maturation.

Two programmable riboregulator systems, based on toehold and three-way junction RNA motifs, were designed and validated as robust translational repressors in cells and applied for the construction of logic gates.

Z-lock is introduced as a new method to control protein activity with light. It relies on a steric block placed over important regions of the target protein that can be released reversibly. Z-lock was applied to regulate cofilin and αTAT activity.

NMR-based structural analysis of the RNA duplex formed by SMN2 exon 7 and U1 snRNA reveals that the splicing modifier SMN-C5 pulls the bulged adenine into the RNA helix base stack and transforms the weak 5ʹ splice site of SMN2 exon 7 into a stronger one.

A crystal structure of the GPCR target of endocannabinoid signaling lipids and drugs, CB1, bound to a negative allosteric modulator (NAM) and an agonist, shows that the NAM binds to a membrane-embedded site reminiscent of the binding site of cholesterol.

Structural and functional analyses of two cytochrome P450 monooxygenases reveal how they catalyze C–N bond formation via a diradical mechanism and are able to accommodate a variety of substrates to form either indolactam or tricyclic products.

Iron is transported from the ventral hippocampus to the medial prefrontal cortex unidirectionally in the brain via axonal projections. This transport is involved in mediating anxiety and the anxiolytic effects of diazepam.

Small molecules that achieve selective PARP1 degradation were developed that block both the catalytic activity and scaffolding effects of PARP1, enabling the decoupling of PARP1 inhibition and PARP1 trapping.

A mitochondrial-targeted acyl protein thioesterase inhibitor enables the identification of ABHD10 as a mitochondrial S-depalmitoylase that acts on the nucleophilic active site residue of peroxiredoxin-5 to modulate its antioxidant capacity.

Crystal structural and biochemical analysis of the chloroplast-localized Holliday junction (HJ) resolvase MOC1 in Zea mays reveals that ZmMOC1 uses a unique β-hairpin structure and a two-metal ion catalysis mechanism to recognize and cleave HJs.