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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.
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.
Plant biologists have recognized the potential in using small molecules identified from chemical libraries to provide insights into biological questions relevant to plants. However, the classical genetics mindset still predominant among plant scientists should evolve to embrace cross-disciplinary chemical genetics projects that will benefit future plant research.
Riboswitches enable microbes to rapidly respond to changing levels of metabolites. A high-throughput platform reveals how RNA structural transitions kinetically compete during transcription in a new mechanism for riboswitch function.
The growth and guidance of axons dictate their trajectories and are critical for neural-circuit formation. Research in this issue uncovers a new mechanism for regulation of axon growth and guidance that acts via extracellular phosphorylation of a receptor.
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.