Cited by 267Per- and polyfluoroalkyl substances researchProtein Interaction Studies and Fluorescence AnalysisPeroxisome Proliferator-Activated Receptors

Structure-Based Investigation on the Interaction of Perfluorinated Compounds with Human Liver Fatty Acid Binding Protein

Zhang, Lianying, Ren, Xiao-Min, Guo, Liang-Hong·2013·Environmental Science & Technology

Abstract

Perfluorinated compounds (PFCs) are known to accumulate in liver and induce hepatotoxicity on experimental animals. Liver fatty acid binding protein (L-FABP) is expressed highly in hepatocytes and binds fatty acids. PFCs may bind with FABP and change their ADME and toxicity profile. In the present study, the binding interaction of 17 structurally diverse PFCs with human L-FABP was investigated to assess their potential disruption effect on fatty acid binding. The binding affinity of twelve perfluorinated carboxylic acids (PFCAs), as determined by fluorescence displacement assay, increased significantly with their carbon number from 4 to 11, and decreased slightly when the number was over 11. The three perfluorinated sulfonic acids (PFSAs) displayed comparable affinity, but no binding was detected for the two fluorotelomer alcohols. Circular dichroism results showed that PFC binding induced distinctive structural changes of the protein. Molecular docking revealed that the driving forces for the binding of PFCs with FABP were predominantly hydrophobic and hydrogen-bonding interactions, and the binding geometry was dependent on both the size and rigidity of the PFCs. Based on the binding constant obtained in this work, the possibility of in vivo competitive displacement of fatty acids from FABP by PFCs was estimated.

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Crossref · 10.1021/es4026722

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  • PFCAs with carbon chain lengths between 10 and 15 may bind to serum proteins and cross the blood-brain barrier in a similar way to saturated fatty acids.

    “hypothesizing that PFCAs with carbon chain lengths between 10 and 15 may be binding to serum proteins and crossing the BBB in a similar way to saturated fatty acids.”
  • In vitro work demonstrates that proteins like human serum albumin and human L-FABP have optimal affinity for PFAS with carbon chain length around 10.

    “This hypothesis is supported by in vitro work demonstrating that proteins like human serum albumin and human L-FABP have optimal affinity for PFAS with carbon chain length around 10 (Zhang et al., 2013; Jackson et al., 2021).”

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Authors
Zhang, L., Ren, X.-M., & Guo, L.-H.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Chinese Academy of Sciences , , P.O. Box 2871, 18 Shuangqing Road , Beijing 100085 ,
Corresponding author
Guo, Liang-Hong
Venue
Environmental Science & Technology
Published
2013-09-05
Volume
47
Issue
19
Pages
11293-11301
ISSN
  • 0013-936X (ISSN-L)
  • 1520-5851
OpenAlex
W2332969818
Cited by
267
References
54
Citations by year
2026: 38 · 2025: 37 · 2024: 23 · 2023: 33 · 2022: 23 · 2021: 24 · 2020: 27 · 2019: 21 · 2018: 11 · 2017: 12 · 2016: 5 · 2015: 5 · 2014: 8
FWCI
4.80
Type
journal article
Language
en
Open access
closed
Locations
  • Environmental Science & Technology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords
perfluorinated compounds, liver fatty acid binding protein, perfluorinated carboxylic acids, perfluorinated sulfonic acids, fluorotelomer alcohols, protein-ligand binding, binding affinity, protein conformational change, hepatotoxicity, carbon chain length effect, hydrophobic interactions, hydrogen bonding
MeSH terms
Fatty Acids, Fluorocarbons, Humans, Alkanesulfonic Acids, Fatty Acid-Binding Proteins

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