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
A metabolic labeling method reveals that genomic N6-methyl-deoxyadenosine in mammalian cell lines originates not from direct methylation in DNA, but from a misincorporation of the metabolite of ribo-N6-methyladenosine.
The authors used an expanded genetic code to incorporate sulfated tyrosine into specific sites of proteins expressed in E. coli and mammalian cells and showed that sulfation of tyrosine at different sites had different functions.
Structural and mutational analysis of three homologous cyclases involved in the biosynthesis of iboga and aspidosperma alkaloids reveals how they convert a common substrate into three distinct scaffolds by controlling regio- and stereoselectivity.
In depsipeptide synthetases, intact adenylation and ketoreductase domains responsible for selecting and reducing α-keto acids are flanked by two halves of a split pseudo-Asub domain whose physical interaction is critical for the module's activity.
The topology of homodimeric membrane protein EmrE is dynamic and includes unassisted flipping of an N-terminal helix in and out of the membrane long after co-translational insertion. Dimerization locks the helix to limit topological dynamics.
A combination of crosslinking, X-ray crystallography, NMR, and mutagenesis provide a detailed visualization of the interactions between an acyl carrier protein and β-ketoacyl-ACP-synthase I in the Escherchia coli fatty acid synthase complex.
An inhibitor of the complement pathway of the innate immune system targets the human complement component 5 protein (C5) by binding to an interfacial pocket to prevent its proteolytic cleavage by the last enzyme of the complement pathway, C5 convertase.
MCC950, a small-molecule inhibitor of the NLRP3 inflammasome, inactivates NLRP3, including hyperactive disease-linked mutations, by closing the ‘open’ conformation, thereby preventing conformational changes required for NLRP3 activation.
MCC950, a small-molecule inhibitor of the NLRP3 inflammasome, interacts directly with NLRP3 at the Walker B motif that hydrolyzes ATP, as defined by a protease-susceptibility assay, mutational analysis, and surface plasmon resonance analysis.
Orange CaMBI, a genetically encoded bioluminescent calcium indicator consisting of calcium-sensing domain CaM, luciferase, and fluorescent proteins, reports calcium dynamics in single cells and reveals calcium oscillations in whole mouse organs.
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.
Transcription factor decoys, DNA molecules designed to mimic regulatory DNAs and prevent repressors binding to their DNA targets, are used to achieve de-repression of silent biosynthetic gene clusters, resulting in production of new natural products.
Engineering of toehold-gated guide RNA (thgRNA) by tethering toehold riboswitches to sgRNAs enables the activation of CRISPR–Cas9 genome editing or transcriptional regulation in response to complementary synthetic or endogenous cellular RNAs.
Structural analysis of prostaglandin E receptor EP3, a member of the prostanoid receptor subfamily of GPCRs, in complex with the endogenous agonist PGE2 reveals important interactions and motions required for receptor activation.
Plant-associated rhizosphere bacteria produce gramibactin, a cyclic lipodepsipeptide siderophore that tightly binds iron via an unexpected functional group, the N-nitrosohydroxylamine (diazeniumdiolate) moieties of the amino acid graminine.
Three homologous cytochrome P450s from monoterpene indole alkaloid-producing plants enable the identification of sarpagan bridge enzyme, which catalyzes either cyclization or aromatization to yield sarpagan or β-carboline alkaloids, respectively.
The antibacterial microvionin contains two new lanthipeptide modifications, a triamino-dicarboxylic acid (avionin) and an N-terminal guanidino fatty acid, that lead to the establishment of the lipolanthine natural product class.
The structure of a monotopic polyprenol phosphate phosphoglycosyl transferase, PglC, reveals how it interacts with the bacterial membrane and coordinates a reaction between membrane-embedded and soluble substrates during glycoconjugate assembly.
The crystal structure of a methyltransferase domain embedded within an interrupted adenylation domain provides insight into how a nonribosomal peptide synthetase N-methylates amino acid precursors for their incorporation into the peptide product.
The discovery of cytochrome P450 monooxygenases that catalyze oxidative demethylation of 6-O-methyl-d-galactose reveals a new activity of cytochrome P450 enzymes and their role in polysaccharide biomass degradation in marine bacteria.
A de novo–designed protein, Syn-F4, hydrolyzes the siderophore ferric enterobactin both in vitro and in Escherichia coli cells, enabling a bacterial strain lacking the essential natural enterobactin esterase to grow in iron-limited medium.
Biosynthesis of the antibiotic sulfazecin involves N-sulfonation in trans of the tripeptide intermediate before synthesis of the β-lactam ring by a noncanonical thioesterase domain, demonstrating a new enzymatic route to the azetidinone moiety.
In Pseudoalteromonas rubra, an unclustered biosynthetic gene encodes a di-iron oxygenase-like enzyme that catalyzes regiospecific C–H activation and cyclization of prodigiosin, yet is unrelated to the Rieske oxygenases that produce other cyclized prodiginines.
A toxic conformation of disease-linked huntingtin protein with expanded polyQ is degraded more slowly than the other conformations, as it is less able to engage the autophagy machinery, explaining its higher toxicity compared to other conformations.
A nonribosomal peptide synthetase involved in colibactin biosynthesis utilizes S-adenosylmethionine as a nonproteinogenic amino acid building block, which is then converted into the cyclopropane moiety that is critical for colibactin's genotoxic activity.
Cpf1 is a CRISPR effector protein that exhibits greater genome editing specificity than Cas9 nuclease. Cpf1 from two distinct bacteria selectively processes RNA polymerase II transcripts into crRNA fragments competent for genome editing.
Characterization of the heme-dependent enzyme KtzT reveals it to be the elusive enzyme responsible for nitrogen–nitrogen bond formation during the biosynthesis of piperazate, a building block for some nonribosomal peptide natural products.
A genetically encoded unnatural amino acid analog and its acidic deprotection enable the site-specific incorporation of phosphotyrosine (pTyr) into proteins such as ubiquitin, where it can be used to study the function of this phosphorylated residue.
Characterization of the gene cluster for omphalotin biosynthesis reveals that they are ribosomally synthesized peptides whose internal α-N-methyl groups are installed by a methyltransferase fused to the precursor peptide substrate.
A synthetic biology system composed of light-wavelength-responsive genetic regulators, signal-processing circuits and pigment-production pathways have resulted in an Escherichia coli strain that can record color images in RGB format.
Most microbial biosynthetic gene clusters are inactive under laboratory culture conditions. A CRISPR–Cas9 genome-editing approach in Streptomyces species enables the targeted activation of silent gene clusters and production of encoded natural products.
Crystallographic analysis of human O-GlcNAc hydrolase (hOGA) fragments containing the catalytic domain, including structures in complex with known inhibitors, suggests that OGA is functional as a dimer and defines opportunities for structure-based drug design.
Crystal structures of human O-GlcNAc hydrolase (hOGA) fragments show that hOGA's dimeric structure is organized by swapping of an α-helical element and reveal features of inhibitor binding to the catalytic domain.
Characterization of a family of Stigonematales (Stig) cyclases that catalyze stereoselective intramolecular C–C bond formation reveals the enzymatic origins of the complex stereochemical patterns in hapalindole and fischerindole alkaloids.
An automated method for solid-phase polypeptide synthesis capitalizes on rapid amide bond formation to enable the production of multiple traditionally difficult-to-synthesize sequences with both high yield and high purity.
Integration of heterologous enzymes into the reaction chambers of fungal fatty acid synthases (FASs) demonstrates the capacity of these megaenzymes for engineered production of short- and medium-chain fatty acids and methyl ketones.
Pharmacological chaperones improve folding of destabilized Escherichia coli dihydrofolate reductase (DHFR) and human disease-linked α-galactosidase A (α-GAL) by biasing the kinetic partitioning between folding, aggregation, and degradation. Chaperoning spares DHFR from aggregation and α-GAL from degradation.
Discovery and characterization of an unusually permissive C-prenyltransferase provides a biocatalytic route for generating novel prenylated compounds, including daptomycin derivatives with increased potency.
A structural study of MraY, an essential enzyme from Clostridium bolteae involved in bacterial cell wall synthesis, in complex with the natural product antibiotic tunicamycin, provides a basis for future antibiotic design.
The combination of an extremely soluble chimeric spider silk protein (spidroin) and a biomimetic spinning method that recapitulates the endogenous pH gradient in silk glands produces a remarkably strong artificial spider silk.
The synergistic effect of the GPCR β2AR on signaling through another GPCR, PTHR, is explained by the release of Gβγ from the heterotrimeric Gαiβγ protein, activating adenylate cyclase AC2 and subsequent prolonged cAMP signaling in internal compartments
The development of small-molecule fluorescent probes through addition of a lipidated cysteine residue next to a caged fluorophore enables detection of endogenous cysteine depalmitoylation by acyl–protein thioesterases in vitro and in live cells.
The iron protein components of bacterial nitrogenases are capable of reducing carbon dioxide (CO2) to carbon monoxide (CO) in the absence of their catalytic partners, mimicking the activity of CO dehydrogenase.