Year: 2025
Type: article
Abstract: Enzyme catalysis is essential for molecular transformations. Here, we make use of amyloid, a fibrillar aggregate formed by stacking peptides with β-sheet, which offers unique selectivity in enzymatic reactions. Azo-stilbene derivative (ASB), the amyloid-recognition motif, is incorporated into the substrate, which allows the amyloid consisting of Bz-Phe-Phe-Ala-Ala-Leu-Leu-NH2 (BL7) to shield the substrates from the approaching enzyme. X-ray crystallographic analysis and structure-shielding effect relationship studies of BL7 reveal that the benzene rings present in the N-terminal benzoyl group and Phe1 side chain are particularly important for the shielding effect on the substrate. The finding results in a selective transformation system in which the reactive site close to ASB is protected by amyloid, while a site far from ASB is converted by the enzymes (trypsin, protein arginine deiminase [PAD], and Staphylococcus aureus V-8 Protease [Glu-C]). Further, the amyloid-shielded enzyme catalysis is compatible with an intact peptide, as the side chain of Tyr can be converted to the amyloid-recognizing motif. The enzymatic reactions combining amyloid provide unique selectivity for molecular transformation which may be used in diverse fields, including in synthetic chemistry. Enzyme catalysis is essential for molecular transformations. Here, the authors show that incorporation of an amyloid recognition motif (azo-stilbene derivative) into the substrate allows the amyloid consisting of Bz-Phe-Phe-Ala-Ala-Leu-Leu-NH2 to shield the substrate from the approaching enzyme.
Source: Nature Communications
Authors: Taka Sawazaki, Fuma Murai, Kai Yamamoto, Daisuke Sasaki, Youhei Sohma
Institution: Wakayama Medical University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1725708031, G2700786945, G2720596666, アミロイドを解明・治療・利用する化学研究, G3978516678, G4299315364, Selective chemical transformation enabled by a unique reaction system through amyloid-substrate complex, Elucidation of structural basis for pathogenicity by a post-translatinally modified TDP-43, an ALS facor, G938635837
OpenAlex ID: W4409147807