Structural mechanisms of QacR induction and multidrug recognition.
Journal Article (Journal Article)
The Staphylococcus aureus multidrug binding protein QacR represses transcription of the qacA multidrug transporter gene and is induced by structurally diverse cationic lipophilic drugs. Here, we report the crystal structures of six QacR-drug complexes. Compared to the DNA bound structure, drug binding elicits a coil-to-helix transition that causes induction and creates an expansive multidrug-binding pocket, containing four glutamates and multiple aromatic and polar residues. These structures indicate the presence of separate but linked drug-binding sites within a single protein. This multisite drug-binding mechanism is consonant with studies on multidrug resistance transporters.
Full Text
Duke Authors
Cited Authors
- Schumacher, MA; Miller, MC; Grkovic, S; Brown, MH; Skurray, RA; Brennan, RG
Published Date
- December 7, 2001
Published In
Volume / Issue
- 294 / 5549
Start / End Page
- 2158 - 2163
PubMed ID
- 11739955
International Standard Serial Number (ISSN)
- 0036-8075
Digital Object Identifier (DOI)
- 10.1126/science.1066020
Language
- eng
Conference Location
- United States