The Structural Basis of Promiscuity in Small Multidrug Resistance Transporters

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Nov 28

PMID 33247110

Citations 24

Authors

Ali A Kermani

Christian B Macdonald

Olive E Burata

B Ben Koff

Akiko Koide

Eric Denbaum

Shohei Koide

Randy B Stockbridge

Affiliations

Soon will be listed here.

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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