1u9n

Crystal structure of the transcriptional regulator EthR in a ligand bound conformation opens therapeutic perspectives against tuberculosis and leprosy

spinqualitylabelsall models 1u9n, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1u9n is a 1 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: CNS, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ETHR_MYCTU Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tetracycline repressor protein 3D structures

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