Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Using biochemical and NMR studies, a class of small-molecule inhibitors termed BAX activation inhibitors were found to bind directly to a previously unrecognized pocket of inactive BAX and allosterically inhibit conformational changes in BAX.
Structural and biochemical analysis of the AtaR–AtaT toxin–antioxin system reveals that AtaR traps AtaT in a precatalytic monomeric state and forms a heterohexameric complex to neutralize AtaT and repress transcription of the operon.
Chemoproteomic mapping of fumarate sensitive cysteines in a hereditary leiomyomatosis and renal cell carcinoma cell line revealed a critical cysteine in the protein–protein interaction interface of the SWI–SNF complex.
Combining X-ray structures, surface plasmon resonance and hydrogen-deuterium exchange–mass spectrometry, a class of highly selective inhibitors was found to bind to an active state of PI3Kγ breaking a conformational ‘lock’ important for activation of PI3Kγ.
The sensitivities of a set of bacterial metal-sensing transcriptional regulators explain how a protein, such as the cobalt chelatase CbiK, is metalated with its cognate metal in cells rather than mis-metalated with more tightly binding metals.
Epigenome profiling in combination with imaging-based chemosensitivity and integrative bioinformatic analysis establishes a method for detecting therapy-induced vulnerabilities, as shown here for ibrutinib-treated chronic lymphocytic leukemia.
An allosteric inhibitor of the proteolytic activity of the CBM signalosome complex scaffolding protein MALT1 acts as a pharmacological chaperone to stabilize a mutant MALT1 carried by an immunodeficient patient.
Single-molecule analysis reveals a novel binding state of Holliday junction (HJ) resolving enzymes where the enzymes partially dissociate from the HJ and allowing nearly unencumbered HJ dynamics, suggesting coupled branch migration and HJ resolution.
Assembly of the mycobacterial cell envelope layers, including peptidoglycan (PG) and the mycomembrane (MM), is synchronous during elongation, when a mobile fraction of the MM diffuses into the septum after thinning of the diffusion barrier formed by PG.
Discovery and exploitation of inherent reaction features of chlorofluoroacetamide (CFA) as a warhead such as low off-target activity and reversible reactivity with cysteine enable specific covalent inhibition of targeted kinases.
A cell-based phenotypic screen identifying inhibitors of Notch signaling led to the discovery of NVS-ZP7-4, which blocks the activity of the zinc transporter SLC39a7 (ZIP7) and induces cell death through an ER stress mechanism.
Screening with a small-molecule reactive-oxygen-species generator identifies the serine hydrolase enzyme ABHD12 as a lipase for the proapoptotic oxidized phoshatidylserine (ox-PS) lipids, which trigger production of proinflammatory cytokines.
The reconstitution of gentamicin B biosynthesis reveals the existence of multiple new intermediates and branching pathways and enables the identification of factors that contribute to the low levels of the natural product in the native producer.
Live-cell imaging and virus trafficking studies show that the host innate immune receptor IFITM3 localizes with endocytic vesicles that fuse with incoming viruses to ultimately enhance their traffic to lysosomes.
A chemoenzymatic tagging approach was developed and identified eukaryotic host proteins that are O-glycosylated by SetA from Legionella. The SetA-consensus motif was applied to recombinant proteins yielding a site-specific O-glucosylation method.
A combination of elicitor screening to induce expression of silent biosynthetic gene clusters with imaging mass spectrometry to visualize the resulting metabolome enables the discovery of nine cryptic natural products.