PUBLICATION
The Affinity of Brominated Phenolic Compounds for Human and Zebrafish Thyroid Receptor β: Influence of Chemical Structure
- Authors
- Kollitz, E.M., De Carbonnel, L., Stapleton, H.M., Ferguson, P.L.
- ID
- ZDB-PUB-180207-23
- Date
- 2018
- Source
- Toxicological sciences : an official journal of the Society of Toxicology 163(1): 226-239 (Journal)
- Registered Authors
- Keywords
- BDE-47, competitive binding assay, endocrine disrupting chemicals, nuclear receptor, tetrabromobisphenol A, tribromophenol
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Binding, Competitive
- Endocrine Disruptors/chemistry*
- Escherichia coli/genetics
- Halogenated Diphenyl Ethers/chemistry*
- Humans
- Ligands
- Phenols/chemistry*
- Polybrominated Biphenyls/chemistry*
- Protein Domains
- Recombinant Proteins/chemistry
- Recombinant Proteins/genetics
- Sequence Alignment
- Structure-Activity Relationship
- Thyroid Hormone Receptors beta/chemistry*
- Thyroid Hormone Receptors beta/genetics
- Transfection
- Triiodothyronine/chemistry
- Triiodothyronine/genetics
- Zebrafish*/genetics
- PubMed
- 29409039 Full text @ Toxicol. Sci.
- CTD
- 29409039
Citation
Kollitz, E.M., De Carbonnel, L., Stapleton, H.M., Ferguson, P.L. (2018) The Affinity of Brominated Phenolic Compounds for Human and Zebrafish Thyroid Receptor β: Influence of Chemical Structure. Toxicological sciences : an official journal of the Society of Toxicology. 163(1):226-239.
Abstract
Brominated phenolic compound (BPCs) are found in the environment, and in human and wildlife tissues, and some are considered to have endocrine disrupting activities. The goal of this study was to determine how structural differences of three BPC classes impact binding affinities for the thyroid receptor beta (TRβ) in humans and zebrafish. BPC classes included halogenated bisphenol A (BPA) derivatives, halogenated oxidative transformation products of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), and brominated phenols. Affinities were assessed using recombinant TRβ protein in competitive binding assays with 125I-triiodothyronine (125I-T3) as the radioligand. Zebrafish and human TRβ displayed similar binding affinities for T3 (Ki = 0.40 and 0.49 nM) and thyroxine (T4, Ki = 6.7 and 6.8 nM). TRβ affinity increased with increasing halogen mass and atomic radius for both species, with the iodinated compounds having the highest affinity within their compound classes. Increasing halogen mass and radius increases the molecular weight, volume, and hydrophobicity of a compound, which are all highly correlated with increasing affinity. TRβ affinity also increased with the degree of halogenation for both species. Human TRβ displayed higher binding affinities for the halogenate BPA compounds, while zebrafish TRβ displayed higher affinities for 2,4,6-trichlorophenol and 2,4,6-trifluorophenol. Observed species differences may be related to amino acid differences within the ligand binding domains. Overall, structural variations impact TRβ affinities in a similar manner, supporting the use of zebrafish as a model for TRβ disruption. Further studies are necessary to investigate how the identified structural modifications impact downstream receptor activities and potential in vivo effects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping