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A class of nepetalactol-related short-chain dehydrogenase/reductases (NEPS) captures a reactive enol intermediate produced by iridoid synthase for cyclization and subsequent oxidation into nepetalactones, the active ingredients in catnip.
HDAC6 modulates acetylation at multiple lysine residues in the N-terminal intrinsically disordered region of RNA helicase DDX3X to regulate liquid–liquid phase separation and stress granule maturation.
The combination of multiple fluorophores on a hybridized DNA scaffold enables the development of the reporter cHOClate, which is used to simultaneously and quantitatively image hypochlorous acid (HOCl) and pH during phagosome maturation.
Prostanoids signal through G-protein-coupled receptors to regulate diverse physiological processes. Structures of three prostanoid receptors in inactive and active conformations now uncover the molecular determinants of ligand recognition and receptor activation and offer new opportunities for drug discovery.
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.
The structure of human prostaglandin E receptor EP4 in complex with antagonist ONO-AE3-208 and a functional antibody reveals a ligand-binding site at the interface of the lipid bilayer that is unique among GPCRs.
Structures of the human thromboxane A2 receptor, a member of the prostanoid family of G-protein-coupled receptors, in complex with two synthetic antagonists reveal that ligands access the ligand-binding pocket from the plane of the lipid bilayer.
Co-opting the amyloid machinery from Bacillus subtilis, engineering of TasA fusion proteins enables the assembly of functionalized biofilms with tunable physicochemical properties that are amenable to 3D printing and microencapsulation techniques.
A structure of the prostaglandin E2 receptor 3 (EP3) bound to the agonist misoprostol shows a completely enclosed binding pocket with a structured water molecule that coordinates misoprostol's ring structure and explains the receptor's selectivity.
A directed evolution approach was applied to optimize a set of 12 small-molecule-responsive biosensors, which led to the engineering of “Marionette” strains of Escherichia coli incorporating these sensors for biotechnological applications.
The observation that transcription activator-like effectors (TALES) displace TALES bound at adjacent downstream DNA enables engineered regulation of gene expression, displacement of other DNA binding proteins and construction of logic-gated systems.
Terpenoids are assembled from five-carbon (C5) units, which limits the available scaffold chemical space for the discovery of bioactive molecules. A combination of enzyme and metabolic engineering now enables biosynthesis of a plethora of non-natural C11 terpenoids.
Yeast engineered to produce the six-carbon terpene building block 2-methyl-geranyl diphosphate, coupled with terpene synthases engineered to accept this noncanonical substrate, enables the biosynthesis of a collection of new C11 terpenoid scaffolds.
The freshwater microcrustacean Daphnia pulex forms defensive neckteeth in response to a collection of chemical cues (the kairomone), now identified as certain fatty acids conjugated to glutamine, released during digestion by its predator Chaoborus.
The HIV protease inhibitor ritonavir targets the calcium-inducing domain (CID) of CD95 to block interactions with PLCγ1. Peptidomimetics targeting the CD95 CID prevents accumulation of inflammatory Th17 cells observed in systemic lupus erythematosus.