- Title
- Interactions of perfluorooctanoic acid with acyl-CoA thioesterase 1 (Acot1)
- Creator
- Liu, Hui; Cheng, Jingjing; Zhou, Yongbing; Liu, Fangfang; Griffin, Nathan; Faulkner, Sam; Wang, Li
- Relation
- Comparative Biochemistry and Physiology Part C: Toxicology and Pharmacology Vol. 250, no. 109159
- Publisher Link
- http://dx.doi.org/10.1016/j.cbpc.2021.109159
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2021
- Description
- Perfluorooctanoic acid (PFOA), a typical representative of per- and polyfluoroalkyl substances (PFASs), is a widely utilized persistent organic pollutant (POP) known to induce liver toxicity in laboratory animals and wildlife. Evidence suggests that PFOA interacts with Acyl-CoA thioesterase 1 (Acot1) to modulate levels of β-oxidation. Specifically, PFOA accelerates β-oxidation, while Acot1 is inhibitory. Few studies have investigated the specific relationship between PFOA and Acot1 and the mechanism of their interaction remains unclear. In the following study, purified rat Acot1 protein was synthesized via bacterial recombination and the structural features that facilitate its binding to PFOA were assessed via molecular docking technology. Additionally, through use of circular dichroism spectroscopy (CD) and isothermal titration calorimetry (ITC) we demonstrate that PFOA binds to WT-Acot1 through electrostatic attraction and low strength non-covalent hydrogen bonding at a molar ratio of 1:1. Furthermore, we identify N326 and H373 amino acid residues as key regulators of the binding process. Together, these findings clarify the interaction pattern of PFOA and Acot1 proteins and provide insight into the specific molecular mechanisms that induce PFOA toxicity in humans and animals.
- Subject
- Acyl-CoA thioesterase 1 (Acot1); perfluorooctanoic acid (PFOA); interaction; toxic mechanism; protein expression
- Identifier
- http://hdl.handle.net/1959.13/1471321
- Identifier
- uon:48647
- Identifier
- ISSN:1532-0456
- Language
- eng
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