The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Structural Mechanisms of QacR Induction and Multidrug Recognition
Abstract
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.
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Cites
PROCHECK: a program to check the stereochemical quality of protein structures
Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993) · Journal of Applied Crystallography · doi:10.1107/s0021889892009944 · Cited by 24,581
Cited by
Crystal structures of a multidrug transporter reveal a functionally rotating mechanism
Murakami, S., Nakashima, R., Yamashita, E., Matsumoto, T., & Yamaguchi, A. (2006) · Nature · doi:10.1038/nature05076 · Cited by 773
Implications of protein flexibility for drug discovery
Teague, S. J. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1129 · Cited by 755
Bacterial multidrug efflux pumps: Mechanisms, physiology and pharmacological exploitations
Sun, J., Deng, Z., & Yan, A. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.05.090 · Cited by 746
Jennings, M. C., Minbiole, K. P. C., & Wuest, W. M. (2015) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.5b00047 · Cited by 651
Regulation of bacterial drug export systems
Grkovic, S., Brown, M. H., & Skurray, R. A. (2002) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.66.4.671-701.2002 · Cited by 423
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Metadata
- Authors
- Schumacher, M. A., Miller, M. C., Grkovic, S., Brown, M. H., Skurray, R. A., & Brennan, R. G.
- Venue
- Science
- Published
- 2001-12-07
- Volume
- 294
- Issue
- 5549
- Pages
- 2158-2163
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1993063963
- Cited by
- 368
- References
- 1
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- closed
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- Schumacher, M. A., Miller, M. C., Grkovic, S., Brown, M. H., Skurray, R. A., & Brennan, R. G. (2001). Structural Mechanisms of QacR Induction and Multidrug Recognition. Science. https://doi.org/10.1126/science.1066020
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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