1. The structural basis of promiscuity in small multidrug resistance transporters.
- Author
-
Kermani AA, Macdonald CB, Burata OE, Ben Koff B, Koide A, Denbaum E, Koide S, and Stockbridge RB
- Subjects
- Amino Acid Sequence, Bacterial Proteins metabolism, Binding Sites, Biological Transport, Crystallography, X-Ray, Escherichia coli metabolism, Gene Transfer, Horizontal, Guanine metabolism, Hydrophobic and Hydrophilic Interactions, Membrane Transport Proteins metabolism, Models, Molecular, Riboswitch, Substrate Specificity, Bacterial Proteins chemistry, Drug Resistance, Multiple, Bacterial, Membrane Transport Proteins chemistry
- 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.
- Published
- 2020
- Full Text
- View/download PDF