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Science 7 December 2001:
Vol. 294. no. 5549, pp. 2158 - 2163
DOI: 10.1126/science.1066020
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Reports

Structural Mechanisms of QacR Induction and Multidrug Recognition

Maria A. Schumacher,1 Marshall C. Miller,1 Steve Grkovic,2 Melissa H. Brown,2 Ronald A. Skurray,2 Richard G. Brennan1*

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.

1 Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97201, USA.
2 School of Biological Sciences, A12, University of Sydney, Sydney NSW 2006, Australia.
*   To whom correspondence should be addressed. E-mail: brennanr{at}ohsu.edu

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