Research articles

An RNAi strategy and a new fluorescent ceramide help identify the transmembrane protein LAPTM4B as facilitating export of ceramide from late endosomes. This activity sensitizes tumor cells to drugs that induce ceramide-driven apoptosis.

An antibiotic biosynthesis monooxygenase (Abm) has been identified in the rice blast fungus Magnaporthe oryzae that converts jasmonic acid into hydroxylated JA, which contributes to pathogenicity through the evasion of host immune response.

Structural and biochemical studies of scavenger decapping enzyme identify conformational changes induced by substrate binding to a second binding site that occur faster than catalytic turnover, such that high substrate concentrations inhibit enzyme activity.

Investigations into the biosynthetic pathways of three families of actin-targeting macrolides lead to insights into their convergent or combinatorial evolution, along with the identification of the first free-living bacterial source of macroalga-derived luminaolides.

Cyclodipeptide synthases use amino acid–loaded tRNAs as substrates to form cyclic peptide dimers. Biochemical and bioinformatic analyses now show that these enzymes are distributed into two phylogenetically distinct major subfamilies and use a broad range of substrates that can be predicted with newly defined sequence motifs.

Montbretin A is a potent inhibitor of amylase, an enzyme critical in starch digestion and thus of relevance for diabetes and obesity. Structural and biochemical analyses now show that a minimal core of the glycoside π-stacks on itself to fit into the active site.

SMASh is a strategy for regulating protein stability, in which treatment with a small molecule targets a protein tagged with a self-removing degron that includes an HCV protease sequence. SMASh was used to target measles virus phosphoprotein P, for which no inhibitors exist.

A bioinformatic and phylogenetic search identifies five enzymes involved in the conversion of DCA to isoDCA in the bacterial bile acid biosynthetic pathway. An investigation of the biological roles of bile acids defines a mutualism between the producer R. gnavus and the nonproducer Bacteroides.

The metal binding domains of P_1B-ATPases regulate transport activity via mostly unknown mechanisms. Structural, biochemical and cellular data now describe one such domain that binds two metals using unusual motifs and with different functional consequences.

Bioinformatic and biochemical analyses define a conserved domain present in the biosynthetic clusters for ribosomally synthesized and post-translationally modified peptides (RiPPs) that recognizes the leader peptide and thus controls downstream processing.

The p30 isoform of C/EBPα associated with leukemia interacts with WDR5, a component of the SET/MLL histone methyltransferase complex. A small molecule, OICR-9429, disrupted p30-WDR5 interactions, resulting in differentiation of p30-expressing leukemia cells.

A bioinformatics pipeline guided by genomic hints of where to look led to the identification and validation of several new classes of self-cleaving ribozymes and several catalytic RNA motifs related to the known hammerhead or HDV ribozymes.

Tus protein bound to Ter sites on circular bacterial chromosomes provides a way to avoid random crashes of opposing replication forks. DNA-unzipping experiments show that the Tus–Ter–induced lock during unzipping at the nonpermissive face requires only DNA-strand separation.

A fusion protein containing P450 and aldo-keto reductase domains is shown to catalyze reticuline isomerization, the critical branch point between the noscapine and morphine biosynthetic pathways. This discovery completes the enzymatic route to morphine and related compounds.

Structural, spectroscopic and kinetic analyses suggest that class II benzoyl-CoA reductases from anaerobic bacteria use an unusual tungsten cofactor and a conserved histidine to perform a reduction akin to the widely used Birch reduction in organic chemistry.

5-Formylcytosine (5fC), produced by TET-mediated oxidation of 5-methylcytosine, is considered an intermediate in active DNA demethylation. Labeling studies and LC/MS analysis across mouse developmental stages reveals that 5fC modifications are more persistent in the genome and may have other functional roles.

Structural and biochemical analysis of the heterocyclase that acts on a ribosomally synthesized and post-translationally modified peptide identifies the basis for leader peptide activation and facilitates engineering of a constitutively active enzyme.

Pseudouridine (ψ) is a C-linked uracil modification originally discovered in tRNA. MS analysis and CeU-Seq, a method that permits chemical tagging, pulldown and sequencing of ψ residues, reveal that these modifications are more abundant in the mammalian transcriptome than previously thought.

Carotenoid biosynthesis requires isomerization of the central double bond. Informatic, spectroscopic and functional characterization of Z-ISO, a protein involved in the process, demonstrates that it is a standalone enzyme with unusual heme-dependent chemistry.

The use of a high-affinity VHL ligand allows the development of chimeric molecules that promote the association of ERRα or RIPK2 with the VHL E3 ubiquitin ligase complex, resulting in protein degradation.