title: Deciphering the action of aromatic effectors on the prokaryotic enhancer-binding protein XylR: a structural model of its N-terminal domain.
abstract: 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 alpha/beta fold, consisting of eight alpha-helices and seven beta-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.
authors.affiliation: Protein Design Group, National Center for Biotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Devos
authors.forename: J
authors.initials: J
authors.lastname: Garmendia
authors.forename: V
authors.initials: V
authors.lastname: de Lorenzo
authors.forename: A
authors.initials: A
authors.lastname: Valencia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011549:Pseudomonas / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014050:Toluene / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry*; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014992:Xylenes / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C080133:DmpR protein, Pseudomonas; D015534:Trans-Activators; D014157:Transcription Factors; C074322:XylR protein, Pseudomonas; D014992:Xylenes; D014050:Toluene; C031285:3-xylene