Linked Life Data

15236969

Source:http://linkedlifedata.com/resource/pubmed/id/15236969

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-7-6
pubmed:databankReference
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
340
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1095-105
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Crystal structure of the TetR/CamR family repressor Mycobacterium tuberculosis EthR implicated in ethionamide resistance.
pubmed:affiliation
School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't