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Despite well-established tumorigenic roles of KRAS mutants, targeting their smooth surfaces was a challenge, which was overcome through the development of G12C-specific covalent inhibitors. A new study shows that optimizing non-covalent interactions with a cryptic pocket produces remarkable potency for another hotspot mutation.
Natural self-cleaving RNAs employ a wide range of catalytic strategies, but it is not known whether artificial ribozymes are capable of the same catalytic diversity. New structures of a methyltransferase ribozyme reveal the potential variety of RNA reactions and mechanisms.
Induced proximity is reshaping drug discovery. A new study debuts deubiquitinase-targeting chimeras (DUBTACs), small bifunctional molecules that co-opt a deubiquitinase to stabilize a target protein.
Pharmacological agents exert their therapeutic effects by altering the biochemical activities of drug targets and, consequently, manipulating cell and organism physiology. A new study combines CRISPR interference with metabolomic profiling to rapidly elucidate drug mechanisms of action.
Just how chaperones clear protein aggregates is a notoriously impenetrable problem. A new study now shows how single-molecule movies of Hsp104 and Hsp70 chaperones acting on amyloid fibers are the key to revealing their underlying cooperation in time and space.
Cell-free biosensing is emerging as an effective and low-cost technology, but interpretation and synthesis of the results remains largely manual. Now, researchers have incorporated a new information-processing layer between biosensors and their outputs using logic gates to integrate complex results.
Inflammasomes are cytosolic immune complexes that initiate inflammatory signaling upon pathogen recognition. A new paper reveals that inhibition of M24B aminopeptidases drives the selective activation of the CARD8 inflammasome, providing new insights into its regulation.
Cryo-EM structures of Mas-related G-protein-coupled receptors (MRGPRs) that are involved in the allergic reaction and itch response reveal structural insights into their activation mechanism, and offer the potential to discover new therapeutic agents for pain and hypersensitivity reactions.
