title: Specific interactions between aryl hydrocarbon receptor and dioxin congeners: ab initio fragment molecular orbital calculations.
abstract: Aryl hydrocarbon receptor (AhR) is a transcription factor and its function is activated by the binding of halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,4-trichlorodibenzo-p-dioxin (TrCDD). TCDD is highly toxic to rat, whereas its congener TrCDD shows only a weak effect on gene expression. In order to elucidate the reason of this remarkable difference in the effect of TCDD and TrCDD, we here obtained stable structures of the complexes with rat AhR (rAhR) and TCDD/TrCDD and investigated their electronic properties by using the ab initio fragment molecular orbital (FMO) method. The results indicate that TCDD binds more strongly to rAhR than TrCDD, which is consistent with the experimentally observed toxicity of TCDD and TrCDD. Furthermore, ab initio FMO calculations elucidate that His324 and Gln381 of rAhR are important for binding TCDD, while His324 and Ser334 are important for TrCDD binding.
authors.affiliation: Department of Knowledge-based Information Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi 441-8580, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Yoshikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyagi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Dedachi
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Ishihara-Sugano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itoh
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kurita
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004583:Electrons; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D013816:Thermodynamics
chemical_list: D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C090523:1,2,4-trichlorodibenzo-1,4-dioxin