Walking over the inflammasome

May 13th, 2019 by Oliver Gorka

Walking over the inflammasome

Nature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0292-8

The NLRP3 inflammasome contributes to pathogenic inflammation in a broad range of diseases, making it a highly relevant drug target. Two studies published in this issue found an inhibitor of NLRP3 inflammasome activation to directly bind NLRP3 within its central NACHT domain, interfering with ATP hydrolysis and structural changes critical for NLRP3 oligomerization and subsequent inflammasome formation.

MCC950 closes the active conformation of NLRP3 to an inactive state

May 13th, 2019 by Ana Tapia-Abellán

MCC950 closes the active conformation of NLRP3 to an inactive state

Nature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0278-6

MCC950, a small-molecule inhibitor of the NLRP3 inflammasome, inactivates NLRP3, including hyperactive disease-linked mutations, by closing the ‘open’ conformation, thereby preventing conformational changes required for NLRP3 activation.

Light-based control of metabolic flux through assembly of synthetic organelles

May 13th, 2019 by Evan M. Zhao

Light-based control of metabolic flux through assembly of synthetic organelles

Nature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0284-8

Optogenetically controlling the assembly of enzyme clusters enhances product formation and specificity during deoxyviolacein biosynthesis by decreasing concentrations of intermediate metabolites and reducing flux through competing pathways.
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MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition

May 13th, 2019 by Rebecca C. Coll

MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition

Nature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0277-7

MCC950, a small-molecule inhibitor of the NLRP3 inflammasome, interacts directly with NLRP3 at the Walker B motif that hydrolyzes ATP, as defined by a protease-susceptibility assay, mutational analysis, and surface plasmon resonance analysis.
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Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme

May 13th, 2019 by Juan Pablo Maianti

Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme

Nature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0271-0

High-throughput screening identifies compounds that target insulin-degrading enzyme (IDE) and X-ray co-crystallography reveals how these compounds block insulin degradation by IDE but support its proteolysis of other substrates, including glucagon.
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Author Correction: In-solution enrichment identifies peptide inhibitors of protein–protein interactions

May 13th, 2019 by Fayçal Touti

Author Correction: In-solution enrichment identifies peptide inhibitors of protein–protein interactions

Nature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0302-x

Author Correction: In-solution enrichment identifies peptide inhibitors of protein–protein interactions
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Author Correction: Affinity-based capture and identification of protein effectors of the growth regulator ppGpp

May 10th, 2019 by Boyuan Wang

Author Correction: Affinity-based capture and identification of protein effectors of the growth regulator ppGpp

Nature Chemical Biology, Published online: 10 May 2019; doi:10.1038/s41589-019-0296-4

Author Correction: Affinity-based capture and identification of protein effectors of the growth regulator ppGpp
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Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis

May 6th, 2019 by Kazuma Sakamoto

Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis

Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis, Published online: 06 May 2019; doi:10.1038/s41589-019-0274-x

Sulfation of chondroitin sulfate and heparan sulfate dictates their abilities to promote axon growth via regulating the binding to the phosphatase PTPRσ and the consequences on phosphorylation of the cortactin component of the autophagy machinery.
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Optical control of sphingosine-1-phosphate formation and function

April 29th, 2019 by Johannes Morstein

Optical control of sphingosine-1-phosphate formation and function

Optical control of sphingosine-1-phosphate formation and function, Published online: 29 April 2019; doi:10.1038/s41589-019-0269-7

A photoswitchable analog of spingosine-1-phosphate (S1P) that allows for modulation of the action of this bioactive lipid exhibits prolonged metabolic stability compared to S1P, activates S1P receptors in cells and mediates nociception in mice.

Biosynthesis of a conserved glycolipid anchor for Gram-negative bacterial capsules

April 29th, 2019 by Liam Doyle

Biosynthesis of a conserved glycolipid anchor for Gram-negative bacterial capsules

Biosynthesis of a conserved glycolipid anchor for Gram-negative bacterial capsules, Published online: 29 April 2019; doi:10.1038/s41589-019-0276-8

Reconstitution of β-Kdo-based capsular polysaccharide biosynthesis and crystallographic analysis of KpsC, a glycosyltransferase with two active sites for β-Kdo-glycolipid primer extension, reveal a new glycosyltransferase structural family.
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