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

Rebecca C. Coll; James R. Hill; Christopher J. Day; Alina Zamoshnikova; Dave Boucher; Nicholas L. Massey; Jessica L. Chitty; James A. Fraser; Michael P. Jennings; Avril A. B. Robertson; Kate Schroder

doi:10.1038/s41589-019-0277-7

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

Rebecca C. Coll, James R. Hill, Christopher J. Day, Alina Zamoshnikova, Dave Boucher, Nicholas L. Massey, Jessica L. Chitty, James A. Fraser, Michael P. Jennings, Avril A. B. Robertson, Kate Schroder

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

602 Citations (Scopus)

3438 Downloads (Pure)

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.

Original language	English
Pages (from-to)	556–559
Journal	Nature Chemical Biology
Volume	15
Early online date	13 May 2019
DOIs	https://doi.org/10.1038/s41589-019-0277-7
Publication status	Published - 01 Jun 2019

Access to Document

10.1038/s41589-019-0277-7Licence: Unspecified

MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2019. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 3.73 MBLicence: Unspecified

Rebecca Coll
- r.collqub.acuk
- School of Medicine, Dentistry and Biomedical Sciences - Lecturer
- Wellcome Wolfson Institute for Experimental Medicine
Person: Academic

Cite this

@article{c2bda4f811294071890aee89260f288d,

title = "MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition",

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.",

author = "Coll, {Rebecca C.} and Hill, {James R.} and Day, {Christopher J.} and Alina Zamoshnikova and Dave Boucher and Massey, {Nicholas L.} and Chitty, {Jessica L.} and Fraser, {James A.} and Jennings, {Michael P.} and Robertson, {Avril A. B.} and Kate Schroder",

year = "2019",

month = jun,

day = "1",

doi = "10.1038/s41589-019-0277-7",

language = "English",

volume = "15",

pages = "556–559",

journal = "Nature Chemical Biology",

issn = "1552-4450",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition

AU - Coll, Rebecca C.

AU - Hill, James R.

AU - Day, Christopher J.

AU - Zamoshnikova, Alina

AU - Boucher, Dave

AU - Massey, Nicholas L.

AU - Chitty, Jessica L.

AU - Fraser, James A.

AU - Jennings, Michael P.

AU - Robertson, Avril A. B.

AU - Schroder, Kate

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41589-019-0277-7

DO - 10.1038/s41589-019-0277-7

M3 - Article

SN - 1552-4450

VL - 15

SP - 556

EP - 559

JO - Nature Chemical Biology

JF - Nature Chemical Biology

ER -

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

Abstract

Access to Document

Fingerprint

Profiles

Rebecca Coll

Cite this