Identification of <i>Chaoborus</i> kairomone chemicals that induce defences in <i>Daphnia</i>

November 14th, 2018 by Linda C. Weiss

Identification of Chaoborus kairomone chemicals that induce defences in Daphnia

Identification of <i>Chaoborus</i> kairomone chemicals that induce defences in <i>Daphnia</i>, Published online: 14 November 2018; doi:10.1038/s41589-018-0164-7

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.
  • Posted in Nat Chem Biol, Publications
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Failure to convert

November 14th, 2018 by Grant Miura

Failure to convert

Failure to convert, Published online: 14 November 2018; doi:10.1038/s41589-018-0172-7

Failure to convert

Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering

November 14th, 2018 by Codruta Ignea

Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering

Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering, Published online: 14 November 2018; doi:10.1038/s41589-018-0166-5

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.
  • Posted in Nat Chem Biol, Publications
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Disrupting the CD95–PLCγ1 interaction prevents Th17-driven inflammation

November 14th, 2018 by Amanda Poissonnier

Disrupting the CD95–PLCγ1 interaction prevents Th17-driven inflammation

Disrupting the CD95–PLCγ1 interaction prevents Th17-driven inflammation, Published online: 14 November 2018; doi:10.1038/s41589-018-0162-9

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.
  • Posted in Nat Chem Biol, Publications
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Expanding the terpenoid kingdom

November 14th, 2018 by Yongjin J. Zhou

Expanding the terpenoid kingdom

Expanding the terpenoid kingdom, Published online: 14 November 2018; doi:10.1038/s41589-018-0167-4

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.

Transcriptional recorder

November 14th, 2018 by Yiyun Song

Transcriptional recorder

Transcriptional recorder, Published online: 14 November 2018; doi:10.1038/s41589-018-0174-5

Transcriptional recorder

Devilish diatoms

November 14th, 2018 by Caitlin Deane

Devilish diatoms

Devilish diatoms, Published online: 14 November 2018; doi:10.1038/s41589-018-0175-4

Devilish diatoms

Metal Enterococcus equipment

November 14th, 2018 by Mirella Bucci

Metal Enterococcus equipment

Metal Enterococcus equipment, Published online: 14 November 2018; doi:10.1038/s41589-018-0173-6

Metal Enterococcus equipment

Structure of human cortisol-producing cytochrome P450 11B1 bound to the breast cancer drug fadrozole provides insights for drug design [Molecular Bases of Disease]

November 13th, 2018 by Simone Brixius-Anderko, Emily E. Scott

Human cytochrome P450 11B1 (CYP11B1) is responsible for the final step generating the steroid hormone cortisol, which controls stress and immune responses and glucose homeostasis. CYP11B1 is a promising drug target to manage Cushing’s disease, a disorder arising from excessive cortisol production. However, the design of selective inhibitors has been hampered because structural information for CYP11B1 is unavailable and the enzyme has high amino acid sequence identity (93%) to a closely related enzyme, the aldosterone-producing CYP11B2. Here we report the X-ray crystal structure of human CYP11B1 (at 2.1 Å resolution) in complex with fadrozole, a racemic compound normally used to treat breast cancer by inhibiting estrogen-producing CYP19A1. Comparison of fadrozole-bound CYP11B1 with fadrozole-bound CYP11B2 revealed that despite conservation of the active site residues, overall structures and active sites had structural rearrangements consistent with distinct protein functions and inhibition. While fadrozole binds to both CYP11B enzymes by coordinating the heme iron, CYP11B2 binds to the R enantiomer of fadrozole, whereas CYP11B1 binds to the S enantiomer, each with distinct orientations and interactions. These results provide insights into the cross-reactivity of drugs across multiple steroidogenic cytochrome P450 enzymes, provide a structural basis for understanding human steroidogenesis, and pave the way for the design of more selective inhibitors of both human CYP11B enzymes.
  • Posted in Journal of Biological Chemistry, Publications
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Transglutaminase inhibition stimulates hematopoiesis and reduces aggressive behavior of crayfish, Pacifastacus leniusculus [Cell Biology]

November 13th, 2018 by Kingkamon Junkunlo, Kenneth Soderhall, Irene Soderhall

Transglutaminase (TGase) is a Ca2+-dependent cross-linking enzyme, which has both enzymatic and non-enzymatic properties. TGase is involved in several cellular activities, including adhesion, migration, survival, apoptosis, and extracellular matrix (ECM) organization. In this study, we focused on the role of the TGase enzyme in controlling hematopoiesis in the crayfish Pacifastacus leniusculus. We hypothesized that a high TGase activity could mediate an interaction of progenitor cells with the ECM to maintain cells in an undifferentiated stage in the hematopoietic tissue (HPT). We found here that the reversible inhibitor cystamine decreases the enzymatic activity of TGase from crayfish HPT as well as from guinea pig in a concentration-dependent manner. Cystamine injection could decrease TGase activity in HPT without affecting production of reactive oxygen species (ROS). Moreover the decrease in TGase activity in the HPT increased the number of circulating hemocytes. Interestingly the cystamine-mediated TGase inhibition reduced aggressive behavior and movement in crayfish. In conclusion, we show that cystamine-mediated TGase inhibition directly releases HPT progenitor cells from the HPT into the peripheral circulation in the hemolymph and strongly reduces aggressive behavior in crayfish.