1U9O

Crystal structure of the transcriptional regulator EthR in a ligand bound conformation

Summary for 1U9O

• Entry DOI: 10.2210/pdb1u9o/pdb
• Related: 1U9N
• Descriptor: Transcriptional repressor EthR, HEXADECYL OCTANOATE (2 entities in total)
• Functional Keywords: tetr family, transcriptional repressor, protein-ligand complex, dna binding protein
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 52579.30

Authors

Frenois, F.,Engohang-Ndong, J.,Locht, C.,Baulard, A.R.,Villeret, V. (deposition date: 2004-08-10, release date: 2004-11-16, Last modification date: 2024-03-13)

Primary citation

Frenois, F.,Engohang-Ndong, J.,Locht, C.,Baulard, A.R.,Villeret, V.
Structure of EthR in a Ligand Bound Conformation Reveals Therapeutic Perspectives against Tuberculosis
Mol.Cell, 16:301-307, 2004

PubMed Abstract: Mycobacterium tuberculosis EthR is a repressor of ethA, a gene encoding a mono-oxygenase required for the activation of the prodrug ethionamide. Here we describe the X-ray crystal structure of EthR, a homodimer with an entirely helical structure showing similarities to TetR family members. Each monomer contained a fortuitous ligand identified as hexadecyl octanoate. The crystal structure of EthR purified in M. smegmatis revealed the presence of a comparable ligand. The binding of hexadecyl octanoate to EthR induces a conformational state incompatible with repressor function, which should lead to ethA derepression and consequently to an increased sensitivity to ethionamide and other thioamides. A related, more hydrophilic ketone was found to exhibit synergistic antimycobacterial effects when tested together with ethionamide, indicating that this strategy may help reduce the dosage of potent antibacterial compounds that otherwise are too toxic to be used as first-line drugs.

PubMed: 15494316
DOI: 10.1016/j.molcel.2004.09.020

Experimental method

X-RAY DIFFRACTION (3.3 Å)