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Aldehyde dehydrogenase 1B1-specific small-molecule inhibitors are identified that block the growth of colon cancer spheroids and organoids and are shown to potentially regulate mitochondrial metabolism and ribosomal function.
Sea stars and sea cucumbers biosynthesize protective glycosylated steroids and triterpenes via divergent oxidosqualene cyclases (OSCs) that produce these distinct saponins in different species as well as in different tissues of a single species.
Using combined methods of modern chemical protein synthesis and structural biology, Ai et al. found a crosstalk mechanism of histone modifications, by which H2BK34ub stimulates the activity of the H3K79 methyltransferase Dot1L through inducing nucleosome distortion.
Biochemical and structural approaches define how the chaperone TAPBPR interacts with MR1 molecules, including empty and ligand-loaded MR1, and facilitates presentation of metabolite-derived antigen ligands by MR1 complexes.
Comprehensive structural biology analysis of seven members of the S1 carbohydrate sulfatase family derived from human gut microbiome Bacteroides reveals mechanisms of glycan recognition and sulfate hydrolysis.
B-cell activation reprograms the TCA cycle and reduces cellular fumarate levels. Increased fumarate caused by fumarase inhibition or dimethyl-fumarate treatment directly succinates and inhibits LYN, leading to impaired B-cell activation and function.
Using isocyanic acid as a CO2 analog generates a stable mimic of lysine carboxylation, enabling development of a quantitative chemoproteomic approach to identify this modification in proteins and explore the lysine carboxylome of a cyanobacterium.
MNK2 was identified as the target of a small molecule named CID661578 that can stimulate pancreatic β-cell generation in zebrafish, pig and human organoids. CID661578 prevents MNK2 from binding to eIF4G in the translation initiation complex.
The zinc-sensor protein Zur in a marine cyanobacterium is distinct from those in other bacteria in structure and location of its sensory zinc site, and facilitates growth across a range of zinc concentrations via activation of a metallothionein gene.
Using nanobodies labeled with FRET fluorophores, the authors show the presence and activation of GPCR mGlu2 and mGlu4 dimers in mouse brain samples and reveal that mGlu2–mGlu4 is the major form of mGlu4-containing dimers outside the cerebellum.
The first crystal structure of human TMPRSS2, a proteolytic driver of SARS-CoV-2 infection in airways and an antiviral target, reveals structural features of viral spike protein and protease inhibitor binding.
Glycomic profiling of mucosal surfaces identified O-mucin glycoconjugate motifs that regulate Candida albicans virulence. Synthetic analogs based on these glycans suppress fungal filamentation, offering potential for antifungal development.
A fungal dioxygenase CcTet displays robust demethylation activity against both N6-methyladenosine (6mA) and 5-methylcytosine on duplex DNA, while its D337F mutant exhibits specific activity against 6mA, providing a useful tool for 6mA functional study.
A redesigned antiviral miniprotein based on a dimeric helix-hairpin motif binds and dimerizes the RBD of the SARS-CoV-2 spike protein and inhibits viral infection by inhibiting spike interaction with ACE2.
A new targeting modality-based transcellular labeling technology called photocatalytic cell tagging enables monitoring of cell–cell interactions when combined with multiomics single-cell sequencing.
A DNA recording method based on an enhanced dCas12a base editor system enables the parallel and scalable recording of cellular signaling events in multiple mammalian cell types.
LRP8 regulation of cellular selenium promotes ferroptosis resistance in cancer. Low selenium leads to ribosome stalling, ribosome collisions and early GPX4 translation termination.
The crystallographic and cryo-EM structures of CB1 bound to the positive allosteric modulator ZCZ011, combined with molecular dynamics simulations and mutagenesis experiments, reveal allosteric modulation of CB1 by rearrangement of the TM2 and TM3 transmembrane domains.
Elucidation of the biosynthetic pathway of the γ-butyrolactone core structure of the furanolide natural product cyanobacterin reveals a carbon–carbon bond-forming cascade that features an enzyme catalyzing a Morita–Baylis–Hillman reaction.
Rather than relying on microbial symbionts, certain corals themselves encode terpene cyclases that produce the eunicellane precursor of defensive terpenes, while the sequences of widespread related cyclase genes indicate a potential ancient origin.