Insights into the solution structure and transcriptional regulation of the MazE9 antitoxin in Mycobacterium tuberculosis

Author:

Roy Tanaya Basu1ORCID,Sarma Siddhartha P.1ORCID

Affiliation:

1. Molecular Biophysics Unit Indian Institute of Science Bangalore Karnataka India

Abstract

AbstractThe present study endeavors to decode the details of the transcriptional autoregulation effected by the MazE9 antitoxin of the Mycobacterium tuberculosis MazEF9 toxin–antitoxin system. Regulation of this bicistronic operon at the level of transcription is a critical biochemical process that is key for the organism's stress adaptation and virulence. Here, we have reported the solution structure of the DNA binding domain of MazE9 and scrutinized the thermodynamic and kinetic parameters operational in its interaction with the promoter/operator region, specific to the mazEF9 operon. A HADDOCK model of MazE9 bound to its operator DNA has been calculated based on the information on interacting residues obtained from these studies. The thermodynamics and kinetics of the interaction of MazE9 with the functionally related mazEF6 operon indicate that the potential for intracellular cross‐regulation is unlikely. An interesting feature of MazE9 is the cistrans conformational isomerization of proline residues in the intrinsically disordered C‐terminal domain of this antitoxin.

Funder

Department of Biotechnology, Ministry of Science and Technology, India

Publisher

Wiley

Subject

Molecular Biology,Biochemistry,Structural Biology

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