Pemk toxin of Bacillus anthracis is a ribonuclease: an insight into its active site, structure, and function

Agarwal, Shivangi ; Mishra, Neeraj Kumar ; Bhatnagar, Sonika ; Bhatnagar, Rakesh (2010) Pemk toxin of Bacillus anthracis is a ribonuclease: an insight into its active site, structure, and function Journal of Biological Chemistry, 285 (10). pp. 7254-7270. ISSN 0021-9258

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Official URL: http://www.jbc.org/content/285/10/7254.short

Related URL: http://dx.doi.org/10.1074/jbc.M109.073387

Abstract

Bacillus anthracis genome harbors a toxin-antitoxin (TA) module encoding pemI (antitoxin) and pemK (toxin). This study describes the rPemK as a potent ribonuclease with a preference for pyrimidines (C/U), which is consistent with our previous study that demonstrated it as a translational attenuator. The in silico structural modeling of the PemK in conjunction with the site-directed mutagenesis confirmed the role of His-59 and Glu-78 as an acid-base couple in mediating the ribonuclease activity. The rPemK is shown to form a complex with the rPemI, which is in line with its function as a TA module. This rPemI-rPemK complex becomes catalytically inactive when both the proteins interact in a molar stoichiometry of 1. The rPemI displays vulnerability to proteolysis but attains conformational stability only upon rPemK interaction. The pemI-pemK transcript is shown to be up-regulated upon stress induction with a concomitant increase in the amount of PemK and a decline in the PemI levels, establishing the role of these modules in stress. The artificial perturbation of TA interaction could unleash the toxin, executing bacterial cell death. Toward this end, synthetic peptides are designed to disrupt the TA interaction. The peptides are shown to be effective in abrogating TA interaction in micromolar range in vitro. This approach can be harnessed as a potential antibacterial strategy against anthrax in the future.

Item Type:Article
Source:Copyright of this article belongs to The American Society for Biochemistry and Molecular Biology.
Keywords:Antimicrobial Peptides; Apoptosis; Drug Resistance/Prokaryotic; Enzymes/Catalysis; Gene; Peptides/Interactions; Toxins; Toxins/Drugs
ID Code:63323
Deposited On:28 Sep 2011 10:31
Last Modified:28 Sep 2011 10:31

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