title: New Targets and Cofactors for the Transcription Factor LrpA from Mycobacterium tuberculosis.
abstract: Rv3291c (MtbLrpA), a transcriptional regulator, belongs to the leucine-responsive regulatory protein (Lrp) family and is thought to play an important role in Mycobacterium tuberculosis persistence. In this study, we verified 17 novel potential binding sites for MtbLrpA by in vitro binding assays on the basis of previous predictions from an in silico analysis and bacterial one-hybrid (BIH) reporter system. Amino acids, such as tyrosine, phenylalanine, tryptophan, and histidine, strongly affect the binding affinity of MtbLrpA, and vitamins, including B1, B3, B6, VC, B7, B9, B12, VA, and VK3, also decrease MtbLrpA binding affinity. This is the first report regarding that an Lrp-like protein can sense vitamins as an environmental signal. Vitamin supplementation to the environment can change the expression level of the target genes, which provides a potential mechanism for tuberculosis supplementary treatment with vitamins.
authors.affiliation: 1 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute , Chinese Academy of Agricultural Sciences, Harbin, China .
authors.forename: Ningning
authors.initials: N
authors.lastname: Song
authors.affiliation: 1 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute , Chinese Academy of Agricultural Sciences, Harbin, China .|2 College of Animal Science and Technology, Jilin Agricultural University , Changchun, China .
authors.forename: Yingying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: 1 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute , Chinese Academy of Agricultural Sciences, Harbin, China .
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Li
authors.affiliation: 1 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute , Chinese Academy of Agricultural Sciences, Harbin, China .
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.affiliation: 1 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute , Chinese Academy of Agricultural Sciences, Harbin, China .
authors.forename: Siguo
authors.initials: S
authors.lastname: Liu
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D001665:Binding Sites; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D051756:Leucine-Responsive Regulatory Protein / Q000037:antagonists & inhibitors / Q000737:chemistry*; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis; D011485:Protein Binding
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; C499616:LrpA protein, bacteria; D051756:Leucine-Responsive Regulatory Protein