Substrate specificity of an actively assembling amyloid catalyst.

Autor: Heier JL; Freie Universität Berlin Department of Biology, Chemistry, Pharmacy Institute of Chemistry and Biochemistry Berlin, Germany., Mikolajczak DJ; Freie Universität Berlin Department of Biology, Chemistry, Pharmacy Institute of Chemistry and Biochemistry Berlin, Germany., Böttcher C; Freie Universität Berlin Department of Biology, Chemistry, Pharmacy Institute of Chemistry and Biochemistry Research Center for Electron Microscopy Berlin, Germany., Koksch B; Freie Universität Berlin Department of Biology, Chemistry, Pharmacy Institute of Chemistry and Biochemistry Berlin, Germany.
Jazyk: angličtina
Zdroj: Biopolymers [Biopolymers] 2017 Jan; Vol. 108 (1).
DOI: 10.1002/bip.23003
Abstrakt: In the presence of Zn 2+ , the catalytic, amyloid-forming peptide Ac-IHIHIQI-NH 2 , was found to exhibit enhanced selectivity for hydrophobic p-nitrophenyl ester substrates while in the process of self-assembly. As opposed to the substrate p-nitrophenyl acetate, which was more effectively hydrolyzed with Ac-IHIHIQI-NH 2 in its fully fibrillar state, the hydrophobic substrate Z-L-Phe-ONp was converted with a second-order rate constant more than 11-times greater when the catalyst was actively assembling. Under such conditions, Z-L-Phe-ONp hydrolysis proceeded at a greater velocity than the more hydrophilic and otherwise more labile ester Boc-L-Asn-ONp. When assembling, the catalyst also showed increased selectivity for the L-enantiomer of Z-Phe-ONp. These findings suggest the occurrence of increased interactions of hydrophobic moieties of the substrate with exposed hydrophobic surfaces of the assembling peptides and present valuable features for future de novo design consideration.
(© 2017 by Wiley Periodicals,Inc.)
Databáze: MEDLINE
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