SNAP output for PDB entry 4fx4 [SNAP web server]

PDB-id

4fx4; SNAP-derived features in text and JSON formats; DNAproDB

Class

transcription regulator-DNA

Method

X-ray (3.1 Å)

Summary

Crystal structure of m. tuberculosis transcriptional regulator mosr (rv1049) in compex with DNA

Reference

Brugarolas P, Movahedzadeh F, Wang Y, Zhang N, Bartek IL, Gao YN, Voskuil MI, Franzblau SG, He C (2012): "The Oxidation-sensing Regulator (MosR) Is a New Redox-dependent Transcription Factor in Mycobacterium tuberculosis." J.Biol.Chem., 287, 37703-37712. doi: 10.1074/jbc.M112.388611.

Abstract

Mycobacterium tuberculosis thrives in oxidative environments such as the macrophage. In order to survive the bacterium must sense and adapt to the oxidative conditions. Several antioxidant defenses including a thick cell wall, millimolar concentrations of small molecule thiols and protective enzymes are known to help the bacterium withstand the oxidative stress. However, oxidation-sensing regulators that control these defenses have remained elusive. In this paper, we report a new oxidation-sensing regulator, Rv1049 or MosR (Mycobacterium tuberculosis oxidation-sensing Regulator). MosR is a transcriptional repressor of the MarR family, which, similarly to B. subtilis OhrR and S. aureus MgrA, dissociates from DNA in the presence of oxidants, enabling transcription. MosR senses oxidation through a pair of cysteines near the N-terminus (Cys10 and Cys12) that upon oxidation forms a disulfide bond. Disulfide formation rearranges a network of hydrogen bonds which leads to a large conformational change of the protein and dissociation from DNA. MosR has been shown previously to play an important role on survival of the bacterium in the macrophage. In this study we show that the main role of MosR is to upregulate expression of rv1050 (a putative exported oxidoreductase that has not yet been characterized) in response to oxidants and propose that it is through this role that MosR contributes to the bacterium survival in the macrophage.