Crystal Structure of an Integron Gene Cassette-Associated Protein from Vibrio cholerae Identifies a Cationic Drug-Binding Module
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Deshpande-2011-Crystal Structure of.pdf
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Author(s)
Deshpande, Chandrika N.
Harrop, Stephen J.
Boucher, Yan
Hassan, Karl A.
Di Leo, Rosa
Xu, Xiaohui
Cui, Hong
Savchenko, Alexei
Chang, Changsoo
Labbate, Maurizio
Date Issued
March 2011
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Deshpande, Chandrika N., et al. (2011) "Crystal Structure of an Integron Gene Cassette-Associated Protein from Vibrio cholerae Identifies a Cationic Drug-Binding Module." PLoS ONE 6(3): e16934.
Version
Final published version
Abstract
Background
The direct isolation of integron gene cassettes from cultivated and environmental microbial sources allows an assessment of the impact of the integron/gene cassette system on the emergence of new phenotypes, such as drug resistance or virulence. A structural approach is being exploited to investigate the modularity and function of novel integron gene cassettes.
Methodology/Principal Findings
We report the 1.8 A crystal structure of Cass2, an integron-associated protein derived from an environmental V. cholerae. The structure defines a monomeric beta-barrel protein with a fold related to the effector-binding portion of AraC/XylS transcription activators. The closest homologs of Cass2 are multi-drug binding proteins, such as BmrR. Consistent with this, a binding pocket made up of hydrophobic residues and a single glutamate side chain is evident in Cass2, occupied in the crystal form by polyethylene glycol. Fluorescence assays demonstrate that Cass2 is capable of binding cationic drug compounds with submicromolar affinity. The Cass2 module possesses a protein interaction surface proximal to its drug-binding cavity with features homologous to those seen in multi-domain transcriptional regulators.
Conclusions/Significance
Genetic analysis identifies Cass2 to be representative of a larger family of independent effector-binding proteins associated with lateral gene transfer within Vibrio and closely-related species. We propose that the Cass2 family not only has capacity to form functional transcription regulator complexes, but represents possible evolutionary precursors to multi-domain regulators associated with cationic drug compounds.
MIT Department
Massachusetts Institute of Technology. Department of Civil and Environmental Engineering
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0016934
