Structural modeling of the ExuR and UxuR transcription factors of E. coli: search for the ligands affecting their regulatory properties

Maria N. Tutukina, Anna V. Potapova, Peter K. Vlasov, Yuri A. Purtov, Olga N. Ozoline

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Gammaproteobacteria get energy for their growth from different carbon sources using either glycolysis or alternative metabolic pathways induced in stress conditions. These metabolic switches are coordinated by complex interplay of regulatory proteins sensing concentrations of available metabolites by mechanisms yet to be understood. Here, we use two transcriptional regulators, ExuR and UxuR, controlling d-galacturonate (d-gal) and d-glucuronate metabolism in Escherichia coli, as the targets for computational search of low-molecular compounds capable to bind their ligand-binding domains. Using a flexible molecular docking, we modeled the interactions of these proteins with substrates and intermediates of glycolysis, Ashwell and Entner–Doudoroff pathways. For UxuR, the two preferred sites of ligand binding were found: one is located within the C-terminal domain, while another occupies the interdomain space. For ExuR, the only one preferred site was detected in the interdomain area. Availability of this area to different ligands suggests that, similar to the Lac repressor, the DNA-binding properties of UxuR and ExuR may be changed by repositioning of their domains. Experimental assays confirmed the ability of ligands with highest affinities to bind the regulatory proteins and affect their interaction with DNA. d-gal that is carried into the cell by the ExuT transporter appeared to be the best ligand for repressor of the exuT transcription, ExuR. For UxuR, the highest affinity was found for d-fructuronate transported by GntP, which biosynthesis is repressed by UxuR. Providing a feedback loop to balance the concentrations of different nutrients, such ligand-mediated modulation can also coordinate switching between different metabolic pathways in bacteria.

Original languageEnglish
Pages (from-to)2296-2304
Number of pages9
JournalJournal of Biomolecular Structure and Dynamics
Issue number10
Publication statusPublished - 2 Oct 2016
Externally publishedYes


  • Escherichia coli
  • ligand-dependent transcriptional factors
  • molecular docking
  • sugar metabolism
  • UxuR and ExuR


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