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.
Potent, selective inhibitors reveal that DAGLβ is a principal 2-AG biosynthetic enzyme and regulates inflammatory processes in mouse peritoneal macrophages.
Riboswitches—RNA motifs that regulate gene expression in response to binding of specific ligands—have been identified for many small-molecule metabolites. An ATP-binding element in the ydaO mRNA of Bacillus subtilis provides the first example of an ATP-responsive riboswitch.
A kinase inhibitor based on a known type II inhibitor allosterically inhibits the RNase activity of IRE1α in vitro and in cells via the ATP-binding site in the kinase domain.
TsrM, a member of the radical SAM enzyme family, is shown to catalyze tryptophan methylation en route to thiostrepton A with the help of a methylcobalamin cofactor and without generating the canonical 5-deoxyadenosyl radical.
Only two of the four glutamates in the selectivity filter of the muscle acetylcholine receptor contribute to the single-channel conductance, with side chain torsional flexibility and microenvironment properties having a previously unrecognized role.
The use of abbreviated pathway constructs leads to trapping of a series of cobalamin intermediates, allowing assignment of the full biosynthetic pathway and defining the roles of CobL as a dual-function methyltransferase and CobE as a likely carrier protein, perhaps facilitating metabolic channeling.
Combined omics techniques lead to the functional assignment of four enzymes involved in a new methionine salvage pathway linking polyamine metabolism with isoprenoid biosynthesis. This reaction sequence involves a homolog of nature's most abundant protein, the CO2-fixing enzyme RubisCO.
EZH2 is a protein methyltransferase component of the polycomb repressive complex 2 (PRC2) that installs the H3K27me3 chromatin mark. EPZ005687 inhibits EZH2 function and H3K27 trimethylation in cells and selectively kills lymphoma cells that require EZH2 for proliferation.
A compound derived from a structure-based screen binds to an allosteric site that includes residues of both the helicase and protease domains of HCV NS3, stabilizing an inactive conformation and inhibiting viral replication.
A systems-pharmacology approach reveals that the combined off-target activity of two kinase inhibitors that impedes MAPK signaling to decrease expression of Myc target genes increases apoptosis in CML cells containing gatekeeper mutations in BCR-ABL.
A new approach for rational enzyme design uses gain-of-function cancer mutations to guide homologous mutations in homoisocitrate dehydrogenase, yielding a biocatalytic path to (R)-2-hydroxyadipate, a precursor for the major commodity chemical adipic acid.
Ferritin controls iron concentrations by storing Fe(III), but the mechanism by which Fe(II) is bound and trafficked into the protein core after oxidation remains controversial. Spectroscopic methods in combination with labeling and competition assays now define a mechanism conserved from archaea to humans.
Mass spectrometric profiling has revealed S-geranylation as a new tRNA modification and identified SelU as the tailoring enzyme in bacterial cells. Nucleotide S-geranylation was found in the anticodon of several tRNAs and regulates translational frameshifting and codon usage.
A small molecule that disrupts interaction between Nur77 and LKB1 leads to LKB1 exit from the nucleus to activate cytoplasmic AMPK and, ultimately, reduces blood glucose and insulin in diabetic mice.
A new global annotation strategy combines sequence identity and genomic context to provide probabilities for all metabolic assignments in a given species. Application of this method leads to multiple new annotations and validation of three enzymatic activities in B. subtilis.
The mechanism for nitro group formation in the thaxtomin family of natural products is unknown. Genetic and biochemical studies now show the cytochrome P450 TxtE catalyzes this direct and regioselective nitration, using NO and O2 to modify a tryptophan indole ring.
Tafazzin, the mitochondrial transacylase that is deficient in Barth syndrome, selects lipid substrates in the inverted hexagonal phase but does not react with bilayer lipids.
Expanding the bacterial toxin-antitoxin system classes to a fifth class, GhoST was found to be involved in maintenance of persister cells, dormant cells that are tolerant of antibiotics. GhoS is the antitoxin, an endoribonuclease that cleaves the toxin mRNA ghoT, whose gene product is a membrane-lytic protein.
C18-ceramide mediates lethal autophagy by anchoring LC3B-II (lipidated LC3) to mitochondrial membranes during mitochondrial fission and thereby recruiting autophagosomes.
A small-molecule activator specific for PKM2 binds to a site distinct from the endogenous activator fructose-1,6-bisphosphate, promoting tetramerization and constitutive activation of PKM2, to inhibit xenograft tumor growth in mice.