Abstract:
:The increase in bacterial resistance to multiple drugs represents a serious and growing health risk. One component of multidrug resistance (MDR) is a group of multidrug transporters that are often regulated at the transcriptional level by repressors and/or activators. Some of these transcription factors are also multidrug-binding proteins, frequently recognizing the same array of drugs that are effluxed by the transporters that they regulate. How a single protein can recognize such chemically disparate compounds is an intriguing question from a structural standpoint and an important question in future drug development endeavours. Unlike the multidrug transporters, the cytosolic multidrug-binding regulatory proteins are more tractable systems for structural analyses. Here, we describe recent crystallographic studies on MarR, BmrR and QacR, three bacterial transcription regulators that are also multidrug-binding proteins. Although our understanding of multidrug binding and transcriptional regulation by MarR is in its initial stages, the structure of a BmrR-TPP+-DNA complex has revealed important insights into the novel transcription activation mechanism of the MerR family, and the structures of a QacR-DNA complex and QacR bound to six different drugs have revealed not only the mechanism of induction of this repressor but has afforded the first view of any MDR protein bound to multiple drugs.
journal_name
Mol Microbioljournal_title
Molecular microbiologyauthors
Schumacher MA,Brennan RGdoi
10.1046/j.1365-2958.2002.03039.xsubject
Has Abstractpub_date
2002-08-01 00:00:00pages
885-93issue
4eissn
0950-382Xissn
1365-2958pii
3039journal_volume
45pub_type
杂志文章,评审abstract::An internal segment of the (p)ppGpp synthetase gene, relA, of Streptomyces coelicolor A3(2) was amplified from genomic DNA using the polymerase chain reaction and used as a hybridization probe to isolate the complete gene from a cosmid library. relA lies downstream of a gene (apt) that apparently encodes adenine phosp...
journal_title:Molecular microbiology
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更新日期:2001-05-01 00:00:00
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pub_type: 评论,杂志文章
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