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Jasmonate derivatives regulate numerous defense and developmental pathways in plants. A chemical screen in Arabidopsis thaliana identified jarin-1 as an inhibitor of jasmonate biosynthesis and a potential chemical probe of jasmonate signaling. The cover features an A. thaliana reporter system used to identify jarin-1, in which successfully transformed individuals (green seedlings) were identified by virtue of their resistance to kanamycin, which otherwise kills them (yellow seedlings). Cover art by Erin Dewalt, based on imagery from Erich Kombrink. Article p830
Development of highly specific kinase inhibitors has been a long-standing challenge in chemical biology. The structural and mechanistic characterization of an Erk1/2 kinase inhibitor provides new strategies to develop specific kinase inhibitors by targeting a binding pocket adjacent to the ATP binding site.
A newly discovered small molecule with broad reactivity against diverse HIV-1 strains prevents the surface envelope glycoprotein from fusing with host cells and offers a potential new anti–HIV-1 target.
Biosynthetic gene clusters encode the enzymatic pathways to make secondary metabolites, molecules of great interest for the pharmaceutical and biotechnology industries. Access to an increasing number of microbial genomes, coupled with efficient bioinformatic tools, is creating new momentum in secondary metabolite research.
Exposure to blue light promotes changes in the protein conformation of flavin photosensors. A review of recent advances in these light sensors discusses key questions in the field and their application to engineer light-mediated molecular switches.
The eukaryotic Elongator complex has been assigned multiple roles in transcription and tRNA modification. In archaea, the Elp3 component is a radical SAM enzyme that catalyzes the carboxymethylation of uridine in the wobble position of tRNA.
Alloswitch-1 is a photoswitchable modulator for mGlu5, and it is the first photoswitchable allosteric GPCR modulator. It was generated by adding the azobenzene Ar-N=N-Ar scaffold into an existing positive allosteric modulator of the receptor.
Production of eukaryotic proteins in bacteria is limited by the specificity of the bacterial oligosaccharyltransferases that perform N-linked glycosylation. ‘GlycoSNAP’ simplifies the study of these enzymes, leading to mutants with relaxed specificity.
A two-enzyme complex works as a cyclodehydratase to form TOMM natural products, but the roles of each protein have been unclear. Structural and biochemical analysis deconvolutes the roles of each protein and identifies a new ATP-binding motif.
Jasmonate derivatives regulate numerous defense and developmental pathways in plants. A chemical screen in Arabidopsis thaliana identifies jarin-1 as an inhibitor of jasmonate biosynthesis and a potential chemical probe of jasmonate signaling.
Metabolic engineering of yeast to incorporate plant and bacterial enzymes that construct and decorate morphine, along with spatial engineering to enable a spontaneous chemical reaction, provides strains capable of producing up to 130 mg/l of opioids.
HIV-1 binds host CD4+ T cells via its gp120 envelope glycoprotein that undergoes changes to allow ‘opening’ of the envelope trimer, exposure of gp41 and binding to the CCR5 co-receptor. Compound 18A inhibits HIV-1 infection by blocking some of these conformational changes.
Crystallographic analysis depicting the interaction of the kinase inhibitor SCH772984 with ERK1/2 reveals a unique binding pocket distinct from off-targets such as haspin and is associated with slow binding kinetics and prolonged inhibitory activity.
Single-molecule measurements show that HSV-1 DNA changes its stiffness by undergoing a solid-to-fluid transition within the capsid in the ionic environment of host cells and at a temperature that is optimal for viral infection.