1t56
From Proteopedia
(New page: 200px<br /><applet load="1t56" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t56, resolution 1.70Å" /> '''Crystal structure of...) |
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| - | [[Image:1t56.gif|left|200px]]<br /><applet load="1t56" size=" | + | [[Image:1t56.gif|left|200px]]<br /><applet load="1t56" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1t56, resolution 1.70Å" /> | caption="1t56, resolution 1.70Å" /> | ||
'''Crystal structure of TetR family repressor M. tuberculosis EthR'''<br /> | '''Crystal structure of TetR family repressor M. tuberculosis EthR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Ethionamide has been used for more than 30 years as a second-line | + | Ethionamide has been used for more than 30 years as a second-line chemotherapeutic to treat tuberculosis patients who have developed resistance to first-line drugs, such as isoniazid (INH) and rifampicin. Activation of the pro-drug ethionamide is regulated by the Baeyer-Villiger monooxygenase EthA and the TetR/CamR family repressor EthR, whose open reading frames are separated by 75 bp on the Mycobacterium tuberculosis genome. EthR has been shown to repress transcription of the activator gene ethA by binding to this intergenic region, thus contributing to ethionamide resistance. We have determined the crystal structure of EthR, to 1.7A resolution, revealing a dimeric two-domain molecule with an overall architecture typical for TetR/CamR repressor proteins. A 20A long hydrophobic tunnel-like cavity in the "drug-binding" domain of EthR is occupied by two 1,4-dioxane molecules, a component of the crystallisation buffer. Comparing the present structure to those of the homologues Staphylococcus aureus QacR and Escherichia coli TetR leads to the hypothesis that the hydrophobic cavity constitutes a binding site for an as yet unknown ligand that might regulate DNA-binding of EthR. |
==About this Structure== | ==About this Structure== | ||
| - | 1T56 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_h37rv Mycobacterium tuberculosis h37rv] with DIO and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1T56 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_h37rv Mycobacterium tuberculosis h37rv] with <scene name='pdbligand=DIO:'>DIO</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T56 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mycobacterium tuberculosis h37rv]] | [[Category: Mycobacterium tuberculosis h37rv]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Besra, G | + | [[Category: Besra, G S.]] |
| - | [[Category: Cocklin, S | + | [[Category: Cocklin, S L.]] |
| - | [[Category: Corsino, P | + | [[Category: Corsino, P E.]] |
| - | [[Category: Daniels, I | + | [[Category: Daniels, I R.]] |
| - | [[Category: Dover, L | + | [[Category: Dover, L G.]] |
[[Category: Futterer, K.]] | [[Category: Futterer, K.]] | ||
[[Category: Tatituri, V.]] | [[Category: Tatituri, V.]] | ||
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[[Category: tetr family]] | [[Category: tetr family]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:10:05 2008'' |
Revision as of 13:10, 21 February 2008
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Crystal structure of TetR family repressor M. tuberculosis EthR
Overview
Ethionamide has been used for more than 30 years as a second-line chemotherapeutic to treat tuberculosis patients who have developed resistance to first-line drugs, such as isoniazid (INH) and rifampicin. Activation of the pro-drug ethionamide is regulated by the Baeyer-Villiger monooxygenase EthA and the TetR/CamR family repressor EthR, whose open reading frames are separated by 75 bp on the Mycobacterium tuberculosis genome. EthR has been shown to repress transcription of the activator gene ethA by binding to this intergenic region, thus contributing to ethionamide resistance. We have determined the crystal structure of EthR, to 1.7A resolution, revealing a dimeric two-domain molecule with an overall architecture typical for TetR/CamR repressor proteins. A 20A long hydrophobic tunnel-like cavity in the "drug-binding" domain of EthR is occupied by two 1,4-dioxane molecules, a component of the crystallisation buffer. Comparing the present structure to those of the homologues Staphylococcus aureus QacR and Escherichia coli TetR leads to the hypothesis that the hydrophobic cavity constitutes a binding site for an as yet unknown ligand that might regulate DNA-binding of EthR.
About this Structure
1T56 is a Single protein structure of sequence from Mycobacterium tuberculosis h37rv with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of the TetR/CamR family repressor Mycobacterium tuberculosis EthR implicated in ethionamide resistance., Dover LG, Corsino PE, Daniels IR, Cocklin SL, Tatituri V, Besra GS, Futterer K, J Mol Biol. 2004 Jul 23;340(5):1095-105. PMID:15236969
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