title: Correlation between TCDD acute toxicity and aryl hydrocarbon receptor structure for different mammals.
abstract: The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity has large species differences, and TCDD exerts its toxicity by binding into aryl hydrocarbon receptor (AHR). In this study, we applied bioinformatics approaches to quantitatively analyze the correlation between TCDD acute toxicity and AHRs. Seven mammalian AHRs were chosen as target receptors. Low conserved functional domains of AHRs were identified and quantitatively characterized. Linear regression was applied to determine the relationships of different mammalian AHRs and TCDD LD(50) values. The results indicated that ligand binding domain and glutamine-rich domain of mammalian AHRs showed a low degree of conservation. Based on previous literatures, the number of glutamine residues (NOQ) and binding free energy with TCDD were applied to quantitatively represent the differences of glutamine-rich domain and ligand binding domain, respectively. Then, regression equations between studied mammalian AHR structures and TCDD LD(50) were constructed, and high linear correlation was found (R(2)=0.986). This study indicated that mammalian differences of TCDD acute toxicity might be partly determined by the differences of glutamine-rich domain and ligand binding domain of AHR, which provides a potential insight to analyze the species differences of TCDD toxicity.
authors.affiliation: Key Laboratory of Integrated Regulation and Resource Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
authors.forename: Qiuying
authors.initials: Q
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Guanghua
authors.initials: G
authors.lastname: Lu
mesh_terms: D000818:Animals; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D007928:Lethal Dose 50; D016014:Linear Models; D008322:Mammals / Q000145:classification; D008958:Models, Molecular; D010802:Phylogeny; D000072317:Polychlorinated Dibenzodioxins / Q000737:chemistry / Q000633:toxicity*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry*
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon