2HH7

Crystal Structure of Cu(I) bound CsoR from Mycobacterium tuberculosis.

2HH7 の概要

• エントリーDOI: 10.2210/pdb2hh7/pdb
• 分子名称: Hypothetical protein CsoR, COPPER (I) ION (3 entities in total)
• 機能のキーワード: 4-helix bundle, unknown function
• 由来する生物種: Mycobacterium tuberculosis
• 細胞内の位置: Cytoplasm (Probable): P71543
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12881.23

構造登録者

Sacchettini, J.C.,Ramesh, A. (登録日: 2006-06-27, 公開日: 2006-12-05, 最終更新日: 2024-02-14)

主引用文献

Liu, T.,Ramesh, A.,Ma, Z.,Ward, S.K.,Zhang, L.,George, G.N.,Talaat, A.M.,Sacchettini, J.C.,Giedroc, D.P.
CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator.
Nat.Chem.Biol., 3:60-68, 2007

PubMed 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 (S(2)N) Cu(I) complex. The 2.6-A 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.

PubMed: 17143269
DOI: 10.1038/nchembio844

実験手法

X-RAY DIFFRACTION (2.55 Å)