7WPG

The 0.90 angstrom X-ray structure of the human heart fatty acid-binding protein complexed with heptanoic acid

7WPG の概要

• エントリーDOI: 10.2210/pdb7wpg/pdb
• 分子名称: Fatty acid-binding protein, heart, heptane-1,1-diol, HEXAETHYLENE GLYCOL, ... (4 entities in total)
• 機能のキーワード: fabp3, complex, binding protein, heptanoic acid, lipid binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15293.55

構造登録者

Sugiyama, S.,Matsuoka, S.,Tsuchikawa, H.,Sonoyama, M.,Inoue, Y.,Hayashi, F.,Murata, M. (登録日: 2022-01-23, 公開日: 2023-01-25, 最終更新日: 2026-06-24)

主引用文献

Maekawa, S.,Takamiya, N.,Terawaki, H.,Kondo, N.,Hayashi, F.,Shimoaka, T.,Matsuoka, S.,Matsumori, N.,Murata, M.,Sonoyama, M.,Sugiyama, S.
Intermolecular interactions of perfluoroalkyl acids with human heart-type fatty acid-binding protein.
Int.J.Biol.Macromol., 369:152710-152710, 2026

PubMed Abstract: PFAS are widely employed in a broad range of applications, spanning from consumer products, such as non-stick cookware, to industrial processes including semiconductor manufacturing. However, PFAS can accumulate in the human body, and certain compounds have been reported to exhibit carcinogenic potential. Perfluoroalkyl acids (PFAAs), a subclass of PFAS, have been shown to bioaccumulate via interactions with fatty acid-binding proteins (FABPs), although the molecular basis for their recognition remains incompletely elucidated. In this study, fluorescence displacement assays revealed that two perfluoroalkyl acids (PFAAs) showed lower apparent IC₅₀ values for human FABP3 than their corresponding physiological ligands, medium-chain fatty acids (MCFAs). We also determined the ultra-high resolution crystal structures of FABP3 in complex with PFAAs and with MCFAs, thereby providing a molecular basis for PFAAs recognition by FABP3. Structural comparisons demonstrated that PFAAs adopt conformations resembling MCFAs but show distinct solvent-coupled features, including close O···F contacts with ordered water molecules in the binding pocket. Our findings suggest that FABP3 recognizes PFAAs through a mechanism partially shared with fatty acids, but not fully explained by hydrophobic effects alone, with possible additional contributions from dipole-interactive effects. This work provides structural insight into PFAS recognition and suggests a molecular basis by which PFAS could interfere with fatty acid binding to FABPs.

PubMed: 42190779
DOI: 10.1016/j.ijbiomac.2026.152710

実験手法

X-RAY DIFFRACTION (0.9 Å)