Deciphering the action of aromatic effectors on the prokaryotic enhancer‐binding protein XylR: a structural model of its N‐terminal domain

Summary The prokaryotic enhancer‐binding protein XylR is the central regulator of the toluene degradation pathway in Pseudomonas species. Copious genetic and biochemical data indicate that the N‐terminal domain of the protein (domain A) interacts directly with m‐ xylene, which renders the protein competent as a transcriptional activator. Single‐site and shuffling mutants of XylR or homologues have been reported to change or expand their effector profiles. Here, we follow a fold recognition approach to generate three‐dimensional models of the domain A of XylR and DmpR with the purpose of deciphering the molecular activity of this protein family. The model is based on the crystallographic data of the rat catechol O‐methyltransferase, a typical α / β fold, consisting of eight α ‐helices and seven β ‐strands. The fold identification is supported by physico‐chemical properties of conserved amino acids, distribution of residues characteristic of the sequence families and confrontation with experimental data. The model not only provides a rationale for understanding published experimental data, but also suggests the molecular mechanism of the activation step and is a potentially useful conceptual tool for designing regulators with predefined inducer specificities.