2HH7
Crystal Structure of Cu(I) bound CsoR from Mycobacterium tuberculosis.
Summary for 2HH7
| Entry DOI | 10.2210/pdb2hh7/pdb |
| Descriptor | Hypothetical protein CsoR, COPPER (I) ION (3 entities in total) |
| Functional Keywords | 4-helix bundle, unknown function |
| Biological source | Mycobacterium tuberculosis |
| Cellular location | Cytoplasm (Probable): P71543 |
| Total number of polymer chains | 1 |
| Total formula weight | 12881.23 |
| Authors | Sacchettini, J.C.,Ramesh, A. (deposition date: 2006-06-27, release date: 2006-12-05, Last modification date: 2024-02-14) |
| Primary citation | 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 Cited by 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: 17143269DOI: 10.1038/nchembio844 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.55 Å) |
Structure validation
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