@article{6f295a93b45c4d15b77e170314940aca,
title = "CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator",
abstract = "Copper is an essential element that becomes highly cytotoxic when concentrations exceed the capacity of cells to sequester the ion. Here, we identify a new copper-specific repressor (CsoR) of a copper-sensitive operon (cso) in Mycobacterium tuberculosis (Mtb) that is representative of a large, previously uncharacterized family of proteins (DUF156). Electronic and X-ray absorption spectroscopies reveal that CsoR binds a single-monomer mole equivalent of Cu(I) to form a trigonally coordinated (S2N) Cu(I) complex. The 2.6-{\AA} crystal structure of copper-loaded CsoR shows a homodimeric antiparallel four-helix bundle architecture that represents a novel DNA-binding fold. The Cu(I) is coordinated by Cys36, Cys65′ and His61′ in a subunit bridging site. Cu(I) binding negatively regulates the binding of CsoR to a DNA fragment encompassing the operator-promoter region of the Mtb cso operon; this results in derepression of the operon in Mtb and the heterologous host Mycobacterium smegmatis. Substitution of Cys36 or His61 with alanine abolishes Cu(I)- and CsoR-dependent regulation in vivo and in vitro. Potential roles of CsoR in Mtb pathogenesis are discussed.",
author = "Tong Liu and Arati Ramesh and Zhen Ma and Ward, {Sarah K.} and Limei Zhang and George, {Graham N.} and Talaat, {Adel M.} and Sacchettini, {James C.} and Giedroc, {David P.}",
note = "Funding Information: We thank N. Echols and T. Alber for their help in the X-ray data collection for the selenomethionine-CsoR crystals, and we thank X. Chen for many helpful discussions. This work was supported by grants from the US National Institutes of Health (GM042569 to D.P.G. and AI068135 to J.C.S.), the Robert A. Welch Foundation (A1295 to D.P.G.) and the US Department of Agriculture (WIS04794 and WIS04823 to A.M.T.). S.K.W. was supported by a US National Institutes of Health Molecular Biosciences Training Grant (T32 GM007215). SSRL is funded by the US Department of Energy and the US National Institutes of Health. The CLS is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC), the National Research Council Canada, the Canadian Institutes of Health Research (CIHR) and the University of Saskatchewan. Research at the University of Saskatchewan was supported by the NSERC and the CIHR, a Canada Research Chair award (G.N.G.), and the University of Saskatchewan, the Province of Saskatchewan, and the US National Institutes of Health (GM057375).",
year = "2007",
month = jan,
doi = "10.1038/nchembio844",
language = "English (US)",
volume = "3",
pages = "60--68",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "Nature Publishing Group",
number = "1",
}