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.
QueE synthesizes a 7-deazapurine structure found in the tRNA base queuosine, the antibiotic toyocamycin and over 30 other natural products. Crystallographic and biochemical studies of QueE now provide molecular insights into the unusual features of this radical SAM enzyme. The cover features the active site of QueE with S-adenosylmethionine, a [4Fe-4S] cluster, a catalytically essential divalent metal cation and a substrate, all queued up for catalysis. Cover art by Erin Dewalt, based on imagery from Daniel Dowling and Catherine Drennan. Article, p106
Lytic polysaccharide mono-oxygenases oxidatively cleave the glycosidic chain on the crystalline surface of cellulose or chitin to create an entry point for hydrolytic cellulases or chitinases. The discovery of a new family of lytic polysaccharide mono-oxygenases expands the possibilities for the use of these enzymes to accelerate biomass degradation.
The mitochondrial permeability transition pore (mPTP) is a multiprotein complex that regulates cell death in multiple pathological conditions. The discovery of new critical components of the mPTP and the identification of anticancer drugs acting on mPTP opens new frontiers for mitochondrial medicine.
Stem cell therapeutics hold great promise, but obtaining optimal cell populations for transplantation remains a major challenge. High-throughput screens of zebrafish embryonic cells have enabled identification of small molecules that can direct the fate of pluripotent stem cells toward tissue-specific progenitors with high therapeutic potential.
Certain adenosine residues within mammalian RNAs undergo reversible N6 methylation. Two methyltransferase enzymes, METTL3 and METTL14, as well as the splicing factor WTAP are identified as core components of the multiprotein complex that deposits RNA N6-methyladenosine (m6A) in nuclear RNAs.
Crystal structures reveal that the antitubercular compound pyridomycin blocks binding of the NADH cofactor to the fatty acid synthesis enzyme InhA while also blocking the lipid substrate–binding pocket.
In synthetic biology designs, circuit components can generally move within the cell, meaning that functional cross-talk can cause faulty wiring. Genome mining, synthetic promoter construction and cross-reactivity screening now identify 20 orthogonal TetR repressor-promoter pairs for use in complex applications.
Crystal structures of QueE, a radical SAM enzyme that converts the purine base of GTP into a deazapurine found in natural products and tRNA, explain how the enzyme functions with a trimmed-down radical SAM enzyme fold and rationalizes its unusual Mg2+ dependency.
Phenotypic screening for serine hydrolase inhibitors capable of modulating lipid storage coupled with target deconvolution identifies carboxylesterase 3 as having a role in regulating adipocyte function, with enzyme inhibition causing positive outcomes in mouse models of obesity and diabetes.
Use of a domain of unknown function as the input for bioinformatic searching reveals a new Cu-dependent family of chitinases, assigned as CAZy group AA11, that diverge in sequence but share structural homology with the existing AA9 and AA10 families.
Crystallographic analysis and spectroscopic studies employing the nitrile moiety of bosutinib as an IR-active probe reveal that structured water molecules, organized by the gatekeeper residues of kinases, mediate the selectivity profile of kinase inhibitor binding.
TR3 is an orphan nuclear receptor with roles in apoptosis. A TR3-binding compound induces mitochondrial translocation of TR3 and autophagy via the Nix–Toms–ANT1/VDAC1 pathway, providing a mechanism for cell death in melanoma cells that are resistant to spontaneous and drug-induced apoptosis.
A screen for compounds that promote ES cell differentiation into pancreatic β cells identified a VMAT2- and monoamine-dependent suppression mechanism of pancreatic β-cell differentiation. VMAT2 inhibitors potentiated differentiation from Pdx1-positive pancreatic progenitor cells into Ngn3-positive endocrine precursors, and then into β cells with increased insulin production.
Substrate binding to the multidrug exporter LmrP from Lactococcus lactis catalyzes proton entrance by stabilizing an outward-open conformation. Transitions between conformational states are dictated by proton passage down the transmembrane helical bundle.
In the ubiquitin-proteasome system, E2 enzymes such as Cdc34A mediate the transfer of ubiquitin to protein substrates, which are thus marked for proteasomal degradation or other fates. New structural data reveal that the small-molecule inhibitor CC0651 impairs Cdc34A activity by stabilizing the normally transient Cdc34A–ubiquitin complex.