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Updated: Apr 19, 2026

Optimized Incorporation of Alkynyl Fatty Acid Analogs for the Detection of Fatty Acylated Proteins using Click Chemistry
Published on: April 9, 2021
Water-mediated recognition of simple alkyl chains by heart-type fatty-acid-binding protein
Shigeru Matsuoka1, Shigeru Sugiyama, Daisuke Matsuoka
1JST-ERATO and Graduate School of Science, Osaka University, Machikaneyama, Toyonaka, Osaka 560-0043 (Japan); Project Research Centre for Fundamental Science, Osaka University, Machikaneyama, Toyonaka, Osaka 560-0043 (Japan).
Abstract:
Long-chain fatty acids (FAs) with low water solubility require fatty-acid-binding proteins (FABPs) to transport them from cytoplasm to the mitochondria for energy production. However, the precise mechanism by which these proteins recognize the various lengths of simple alkyl chains of FAs with similar high affinity remains unknown. To address this question, we employed a newly developed calorimetric method for comprehensively evaluating the affinity of FAs, sub-Angstrom X-ray crystallography to accurately determine their 3D structure, and energy calculations of the coexisting water molecules using the computer program WaterMap. Our results clearly showed that the heart-type FABP (FABP3) preferentially incorporates a U-shaped FA of C10-C18 using a lipid-compatible water cluster, and excludes longer FAs using a chain-length-limiting water cluster. These mechanisms could help us gain a general understanding of how proteins recognize diverse lipids with different chain lengths.
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