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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.
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.
Microbiota-derived butyrate acylation of the key Salmonella enterica transcriptional regulator HilA attenuates virulence of the bacteria, blocking invasion of epithelial cells in vitro and dissemination in vivo.
A structural look at the interaction between the SH3b domain of the peptidoglycan endopeptidase lysostaphin and the target for its antistaphylococcal activity, peptidoglycan, reveals a mechanism of bacterial cell wall binding.
Cryo-EM and crystal structural analysis of DDB1–DCAF15–DDA1 in complex with E7820 and RBM39 reveal that aryl-sulfonamides reshape the surface of the cullin RING ligase substrate receptor DCAF15 to bind and degrade the splicing factor RBM39.
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.
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 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.
Ancestral protein reconstruction followed by biochemical and structural analyses characterizes the evolutionary trajectory of methyl-parathion hydrolase from an ancestral dihydrocoumarin hydrolase through the accumulation of five key mutations.
A dimerization-induced self-quenching fluorescent dye, Gemini-561, and its aptamer o-Coral were developed for imaging mRNAs in living cells with improved brightness and photostablility.
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.
The authors characterize the cotranscriptional folding of the Clostridium beijerinckii pfl ZTP riboswitch in response to its ligand ZMP, and reveal that an internal RNA strand displacement and riboswitch sequence play important roles in the process.
Rather than operating linearly like most NRPS–PKS systems, biosynthesis of the thalassospiramide lipopeptides employs intermodule substrate activation and tailoring, module skipping and pass-back chain extension to generate chemical diversity.
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.
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.
Synthetic microbial consortia were applied to demonstrate that oscillatory gene expression in a bacterial population can be propagated over longer distances by activating a localized positive feedback loop.
A phenotypic screen led to the identification of potent inhibitors of mouse BAK-driven apoptosis. The compounds interact with VDAC2 and stabilize its interaction with BAK, blocking apoptosis at an early stage to preserve long-term cell survival.
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.
A light-activated RNA labeling method was developed to determine spatial organization of a transcriptome and found that ribosomal proteins and oxidative phosphorylation pathway proteins are highly enriched at the outer mitochondrial membrane.
Zebrafish p63 isoforms were identified as thalidomide-dependent neosubstrates of the cereblon-containing E3 ligase complex. ∆Np63α and TAp63α are responsible for thalidomide-induced malformations of pectoral fins and otic vesicles, respectively.