Structural mechanisms of QacR induction and multidrug recognition.

Published

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 2001

Published In

Volume / Issue

  • 294 / 5549

Start / End Page

  • 2158 - 2163

PubMed ID

  • 11739955

Pubmed Central ID

  • 11739955

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1066020

Language

  • eng