3 years ago

Switchable Hydrolase Based on Reversible Formation of Supramolecular Catalytic Site Using a Self-Assembling Peptide

Switchable Hydrolase Based on Reversible Formation of Supramolecular Catalytic Site Using a Self-Assembling Peptide
Rein V. Ulijn, Tong Wang, Charalampos G. Pappas, Chunqiu Zhang, Vishal Narang, Ayala Lampel, Douglas MacPherson, Ramim Shafi, Charles Maldarelli
The reversible regulation of catalytic activity is a feature found in natural enzymes which is not commonly observed in artificial catalytic systems. Here, we fabricate an artificial hydrolase with pH-switchable activity, achieved by introducing a catalytic histidine residue at the terminus of a pH-responsive peptide. The peptide exhibits a conformational transition from random coil to β-sheet by changing the pH from acidic to alkaline. The β-sheet self-assembles to form long fibrils with the hydrophobic edge and histidine residues extending in an ordered array as the catalytic microenvironment, which shows significant esterase activity. Catalytic activity can be reversible switched by pH-induced assembly/disassembly of the fibrils into random coils. At higher concentrations, the peptide forms a hydrogel which is also catalytically active and maintains its reversible (de-)activation. A pH-switchable artificial hydrolase was constructed by introducing a catalytic histidine residue to a pH-responsive β-hairpin peptide (VK2H). The conformation of VK2H can be regulated between random coil and β-sheet fibrils by the pH. The catalytic activity follows the self-assembly “switch” by the reversible alignment of catalytic and binding sites with the unassembled random coils inactive and the fibrils able to catalyze the hydrolysis of substrate.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201708036

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