Covalent Catalysis by Cross β Amyloid Nanotubes

Area of Science:

• Biomaterials Science
• Synthetic Biology
• Protein Engineering

Background:

• Enzyme active sites utilize precise amino acid positioning for catalysis via covalent and non-covalent interactions.
• Nature employs reversible covalent anchoring for enzyme activation and biological processes like visual phototransduction.

Purpose of the Study:

• To construct paracrystalline amyloid surfaces mimicking enzyme binding pockets.
• To investigate the catalytic activity of designed amyloid nanotubes in ester hydrolysis.

Main Methods:

• Self-propagation of short peptides to form amyloid nanotubes.
• Incorporation of lysine residues within amyloid structures to create catalytic sites.
• Hydrolysis assays using activated and inactivated esters to assess catalytic efficiency.
• Mutational analysis of lysine residues to confirm their role in catalysis.

Main Results:

• Homogeneous amyloid nanotubes with exposed arrays of imidazoles and lysines were successfully constructed.
• The designed amyloid nanotubes efficiently hydrolyzed both activated and inactivated esters via Schiff imine formation mediated by lysines.
• Mutating lysines to charged residues resulted in similar morphologies but abolished the catalytic rate enhancement.

Conclusions:

• Designed amyloid microphases can mimic the binding pockets of advanced proteins.
• Amyloid nanotubes offer a platform for developing functional materials with catalytic properties.
• This work provides insights into the origins of enzyme catalytic mechanisms.