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The cover depicts infection of an Arabidopsis plant by the fungus Botrytis cinerea. Jasmonylisoleucine is a phytohormone that regulates plant defense against fungal pathogens and whose synthesis was thought to be dependent on OPDA reductase 3 (OPR3) activity. An OPR3-indendent pathway was identified that produces 4,5-didehydrojasmonate as a precursor for jasmonyl-isoleucine. Cover design by Erin Dewalt, based on an image taken by Andrea Chini. Article, p171; News & Views, p109
The central dogma processes of DNA replication, transcription, and translation are responsible for the maintenance and expression of every gene in an organism. An orthogonal central dogma may insulate genetic programs from host regulation and allow expansion of the roles of these processes within the cell.
By integrating metagenomics, spectroscopy and synthetic biology, the individualized chemistry of small reef-dwelling organisms and their associated microbiota can be characterized in exquisite detail, unlocking a wealth of structural diversity for the development of new drugs.
The lipid-derived hormone jasmonate promotes durable resistance of plants to a myriad of herbivores and pathogens. New evidence reveals an alternative pathway for the terminal steps of jasmonate biosynthesis and further advances our understanding of bioactive oxylipins in the plant kingdom.
A potent and specific small-molecule inhibitor of a long-sought-after anticancer drug target, USP7, that acts allosterically to inhibit MDM2-stabilizing activity foretells of more allosteric inhibitors for deubiquitinases and E3 ligases.
Selections with a phage-displayed antibody library against an existing protein–small-molecule complex enabled the generation of antibody-based chemically induced dimerizers (AbCIDs) with the properties necessary for use in regulating cell therapies.
A selective inhibitor of the deubiquitinase USP7 binds an allosteric site to inhibit its MDM2-stabilizing activity, resulting in stabilization of p53 and p21, which confers hypersensitivity to cancer cells for killing by the compound.
D2 dopamine receptor ligands biased for b-arrestin recruitment were developed based on a receptor homology model that identified conserved ligand contacts within the TM5 and EL2 regions as important for biased signaling.
A potent inhibitor of the conditionally essential mitochondrial phosphate carrier protein Mir1 in the fungi Candida albicans diminishes mitochondrial oxygen consumption and causes dramatic changes in concentrations of citrate and succinate.
Two complementary coiled-coil peptides and a bacterial microcompartment shell protein are combined to construct cytoscaffolds within Escherichia coli cells. Targeting enzymes to the cytoplasmic scaffold results in colocalization and improved metabolic flux.
Cytosolic 2-Cys peroxiredoxins can enable, rather than compete with, rapid thiol oxidation by relaying H2O2-derived oxidizing equivalents to other proteins, suggesting a broadened role for peroxiredoxins as sensors and transmitters of H2O2 signals.
A modular protein expression system enables the structural and functional characterization of human glycosyltransferases, glycoside hydrolases and other carbohydrate-modifying enzymes.
A selective small-molecule degrader of CDK9 was generated by conjugating an imide to SNS-032, a promiscuous ATP-site-directed CDK binder. The pharmacological consequences of CDK9 degradation versus inhibition were compared.
OPR3 is required to reduce the JA-Ile precursor OPDA. Analyses of JA levels in a loss-of-function opr3-3 mutant identified an OPR3-independent pathway for JA-Ile biosynthesis, based on OPDA conversion to 4,5-ddh-JA and reduction to JA by OPR2.
A combination of spectroscopy, metagenomics, and synthetic biology enables the characterization of the antiviral divamides, a class of lanthipeptide natural products in which even minor changes in structure lead to different biological activities.