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MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition
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MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition
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Journal Article
MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition
2019
Overview
Inhibition of the NLRP3 inflammasome is a promising strategy for the development of new treatments for inflammatory diseases. MCC950 is a potent and specific small-molecule inhibitor of the NLRP3 pathway, but its molecular target is not defined. Here, we show that MCC950 directly interacts with the Walker B motif within the NLRP3 NACHT domain, thereby blocking ATP hydrolysis and inhibiting NLRP3 activation and inflammasome formation.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Adenosine Triphosphate - antagonists & inhibitors
/ Adenosine Triphosphate - metabolism
/ Binding Sites - drug effects
/ Chemistry and Materials Science
/ Heterocyclic Compounds, 4 or More Rings - chemistry
/ Heterocyclic Compounds, 4 or More Rings - pharmacology
/ Humans
/ Inflammasomes - antagonists & inhibitors
/ Inflammasomes - biosynthesis
/ NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors
/ NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
