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Kermani, Ali A; Macdonald, Christian B; Burata, Olive E; Ben Koff, B; Koide, Akiko; Denbaum, Eric; Koide, Shohei; Stockbridge, Randy B
Nature communications, 11/2020, Letnik: 11, Številka: 1Journal Article
By providing broad resistance to environmental biocides, transporters from the small multidrug resistance (SMR) family drive the spread of multidrug resistance cassettes among bacterial populations. A fundamental understanding of substrate selectivity by SMR transporters is needed to identify the types of selective pressures that contribute to this process. Using solid-supported membrane electrophysiology, we find that promiscuous transport of hydrophobic substituted cations is a general feature of SMR transporters. To understand the molecular basis for promiscuity, we solved X-ray crystal structures of a SMR transporter Gdx-Clo in complex with substrates to a maximum resolution of 2.3 Å. These structures confirm the family's extremely rare dual topology architecture and reveal a cleft between two helices that provides accommodation in the membrane for the hydrophobic substituents of transported drug-like cations.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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