Structural mechanisms of multidrug recognition and regulation by bacterial multidrug transcription factors.

Published

Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Schumacher, MA; Brennan, RG

Published Date

  • August 2002

Published In

Volume / Issue

  • 45 / 4

Start / End Page

  • 885 - 893

PubMed ID

  • 12180910

Pubmed Central ID

  • 12180910

International Standard Serial Number (ISSN)

  • 0950-382X

Digital Object Identifier (DOI)

  • 10.1046/j.1365-2958.2002.03039.x

Language

  • eng

Conference Location

  • England