Rebecca C. Coll, James R. Hill, C. Day
May 13, 2019
Citations
16
Influential Citations
500
Citations
Quality indicators
Journal
Nature Chemical Biology
Abstract
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.