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Title: ClbM is a versatile, cation-promiscuous MATE transporter found in the colibactin biosynthetic gene cluster

Abstract

Multidrug transporters play key roles in cellular drug resistance to toxic molecules, yet these transporters are also involved in natural product transport as part of biosynthetic clusters in bacteria and fungi. The genotoxic molecule colibactin is produced by strains of virulent and pathobiont Escherichia coli and Klebsiella pneumoniae. In the biosynthetic cluster is a multidrug and toxic compound extrusion protein (MATE) proposed to transport the prodrug molecule precolibactin across the cytoplasmic membrane, for subsequent cleavage by the peptidase ClbP and cellular export. We recently determined the X-ray structure of ClbM, and showed preliminary data suggesting its specific role in precolibactin transport. Here, we define a functional role of ClbM by examining transport capabilities under various biochemical conditions. Our data indicate ClbM responds to sodium, potassium, and rubidium ion gradients, while also having substantial transport activity in the absence of alkali cations. - Highlights: • ClbM is a cation promiscuous MATE multidrug transporter. • The role of key residues were identified in both the cation and proton binding. • The biologically relevant substrate for ClbM is the natural product precolibactin.

Authors:
;  [1]; ;  [2]
  1. Department of Chemistry, University of Florida, Gainesville, FL, 32611 (United States)
  2. Department of Medicine, University of Florida, Gainesville, FL, 32611 (United States)
Publication Date:
OSTI Identifier:
22696801
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 482; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CATIONS; ESCHERICHIA COLI; MOLECULES; TOXICITY; X RADIATION

Citation Formats

Mousa, Jarrod J., Newsome, Rachel C., Yang, Ye, Jobin, Christian, and Bruner, Steven D., E-mail: bruner@ufl.edu. ClbM is a versatile, cation-promiscuous MATE transporter found in the colibactin biosynthetic gene cluster. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2016.12.018.
Mousa, Jarrod J., Newsome, Rachel C., Yang, Ye, Jobin, Christian, & Bruner, Steven D., E-mail: bruner@ufl.edu. ClbM is a versatile, cation-promiscuous MATE transporter found in the colibactin biosynthetic gene cluster. United States. doi:10.1016/J.BBRC.2016.12.018.
Mousa, Jarrod J., Newsome, Rachel C., Yang, Ye, Jobin, Christian, and Bruner, Steven D., E-mail: bruner@ufl.edu. Sun . "ClbM is a versatile, cation-promiscuous MATE transporter found in the colibactin biosynthetic gene cluster". United States. doi:10.1016/J.BBRC.2016.12.018.
@article{osti_22696801,
title = {ClbM is a versatile, cation-promiscuous MATE transporter found in the colibactin biosynthetic gene cluster},
author = {Mousa, Jarrod J. and Newsome, Rachel C. and Yang, Ye and Jobin, Christian and Bruner, Steven D., E-mail: bruner@ufl.edu},
abstractNote = {Multidrug transporters play key roles in cellular drug resistance to toxic molecules, yet these transporters are also involved in natural product transport as part of biosynthetic clusters in bacteria and fungi. The genotoxic molecule colibactin is produced by strains of virulent and pathobiont Escherichia coli and Klebsiella pneumoniae. In the biosynthetic cluster is a multidrug and toxic compound extrusion protein (MATE) proposed to transport the prodrug molecule precolibactin across the cytoplasmic membrane, for subsequent cleavage by the peptidase ClbP and cellular export. We recently determined the X-ray structure of ClbM, and showed preliminary data suggesting its specific role in precolibactin transport. Here, we define a functional role of ClbM by examining transport capabilities under various biochemical conditions. Our data indicate ClbM responds to sodium, potassium, and rubidium ion gradients, while also having substantial transport activity in the absence of alkali cations. - Highlights: • ClbM is a cation promiscuous MATE multidrug transporter. • The role of key residues were identified in both the cation and proton binding. • The biologically relevant substrate for ClbM is the natural product precolibactin.},
doi = {10.1016/J.BBRC.2016.12.018},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 482,
place = {United States},
year = {2017},
month = {1}
}