1u9o
From Proteopedia
(New page: 200px<br /><applet load="1u9o" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u9o, resolution 3.3Å" /> '''Crystal structure of ...) |
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| - | [[Image:1u9o.gif|left|200px]]<br /><applet load="1u9o" size=" | + | [[Image:1u9o.gif|left|200px]]<br /><applet load="1u9o" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1u9o, resolution 3.3Å" /> | caption="1u9o, resolution 3.3Å" /> | ||
'''Crystal structure of the transcriptional regulator EthR in a ligand bound conformation'''<br /> | '''Crystal structure of the transcriptional regulator EthR in a ligand bound conformation'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mycobacterium tuberculosis EthR is a repressor of ethA, a gene encoding a | + | 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== | ==About this Structure== | ||
| - | 1U9O is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with CNS as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1U9O is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=CNS:'>CNS</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U9O OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Baulard, A | + | [[Category: Baulard, A R.]] |
[[Category: Engohang-Ndong, J.]] | [[Category: Engohang-Ndong, J.]] | ||
[[Category: Frenois, F.]] | [[Category: Frenois, F.]] | ||
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[[Category: transcriptional repressor]] | [[Category: transcriptional repressor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:22:05 2008'' |
Revision as of 13:22, 21 February 2008
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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 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
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