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2020 - The structural basis of promiscuity in small multidrug resistance transporters

 Icon N1   SURFE2R N1 publication in Nature Communications (2020)

Authors:
Kermani A.A., Macdonald C.B., Burata O.E., Koff B.B., Koide A., Denbaum E., Koide S., Stockbridge R.B.

Journal
Nature Communications (2020) doi: 10.1038/s41467-020-19820-8


Abstract:

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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