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1u9o
From Proteopedia
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Crystal structure of the transcriptional regulator EthR in a ligand bound conformation
Overview
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.
About this Structure
1U9O is a Protein complex structure of sequences from Mycobacterium tuberculosis with CNS as ligand. Full crystallographic information is available from OCA.
Reference
Structure of EthR in a ligand bound conformation reveals therapeutic perspectives against tuberculosis., Frenois F, Engohang-Ndong J, Locht C, Baulard AR, Villeret V, Mol Cell. 2004 Oct 22;16(2):301-7. PMID:15494316
Page seeded by OCA on Sun Nov 25 03:34:54 2007
