7FBF

The 0.86 angstrom X-ray structure of the human heart fatty acid-binding protein complexed with octanoic acid

Summary for 7FBF

• Entry DOI: 10.2210/pdb7fbf/pdb
• Descriptor: Fatty acid-binding protein, heart, OCTANOIC ACID (CAPRYLIC ACID), HEXAETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: fabp, complex, binding protein, octanoic acid, lipid binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 15305.56

Authors

Sugiyama, S.,Kakinouchi, K.,Matsuoka, S.,Tsuchikawa, H.,Sonoyama, M.,Inoue, Y.,Hayashi, F.,Murata, M. (deposition date: 2021-07-09, release date: 2022-07-13, Last modification date: 2026-06-24)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (0.86 Å)