Amyloid-reoriented enzyme catalysis.

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.