Pyrazinamide triggers degradation of its target aspartate decarboxylase

Pooja Gopal; Jickky Palmae Sarathy; Michelle Yee; Priya Ragunathan; Joon Shin; Shashi Bhushan; Junhao Zhu; Tatos Akopian; Olga Kandror; Teck Kwang Lim; Martin Gengenbacher; Qingsong Lin; Eric J. Rubin; Gerhard Grüber; Thomas Dick

doi:10.1038/s41467-020-15516-1

Nature Communications (Apr 2020)

Pyrazinamide triggers degradation of its target aspartate decarboxylase

Pooja Gopal,
Jickky Palmae Sarathy,
Michelle Yee,
Priya Ragunathan,
Joon Shin,
Shashi Bhushan,
Junhao Zhu,
Tatos Akopian,
Olga Kandror,
Teck Kwang Lim,
Martin Gengenbacher,
Qingsong Lin,
Eric J. Rubin,
Gerhard Grüber,
Thomas Dick

Affiliations

Pooja Gopal: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore
Jickky Palmae Sarathy: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore
Michelle Yee: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore
Priya Ragunathan: School of Biological Sciences, Nanyang Technological University
Joon Shin: School of Biological Sciences, Nanyang Technological University
Shashi Bhushan: School of Biological Sciences, Nanyang Technological University
Junhao Zhu: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University
Tatos Akopian: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University
Olga Kandror: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University
Teck Kwang Lim: Department of Biological Sciences, National University of Singapore
Martin Gengenbacher: Center for Discovery and Innovation, Hackensack Meridian Health
Qingsong Lin: Department of Biological Sciences, National University of Singapore
Eric J. Rubin: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University
Gerhard Grüber: School of Biological Sciences, Nanyang Technological University
Thomas Dick: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore

DOI: https://doi.org/10.1038/s41467-020-15516-1
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 10

Abstract

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It has been shown that the bioactive component of pyrazinamide, pyrazinoic acid (POA), blocks coenzyme A biosynthesis in M. tuberculosis by binding to the aspartate decarboxylase PanD. Here the authors show that pyrazinamide triggers degradation of PanD by stimulating its degradation by the caseinolytic protease Clp.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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