Catalytically Diverse Cross β Amyloid

Chatterjee, Ayan (2022) Catalytically Diverse Cross β Amyloid. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Ayan Chatterjee (17RS014)) 17RS014.pdf - Submitted Version Restricted to Repository staff only Download (16MB)

Abstract

During the billions of years of the evolutionary journey, rudimentary protopolymers, involved in primitive metabolic pathways with low catalytic activity played critical roles in the emergence of modern enzymes that have remarkable substrate specificity. In depth study of primitive polymers such as short peptide-based amyloids, often argued as the earliest protein folds due to their inherent repetitive β sheet structures, could be interesting in discerning the prebiotic origins of catalytically active binding pockets of advanced proteins. In this context, the present thesis, “Catalytically Diverse Cross β Amyloid,” deals with the investigation of the catalytic potential and versatility of short peptide based cross β rich folds towards promoting a diverse set of chemical transformations. These minimal peptide-based catalytic systems have been judiciously utilized to foster two-step, multistep to complex cascade reaction networks with emergent multimodal functions, foreshadowing the complex cascade-mediated functionalities seen in extant biochemistry. Further, the thesis reports the generation of short peptide-based dynamic coacervates that can bind guest (catalysts) and concomitantly modulate their activity. In this context, Chapter 1 briefly introduces short peptide-based amyloids with their relevance as a primitive protein fold for diverse catalytic traits and associated up-to-date literature review. Chapter 2 presents histidine exposed cross β amyloid nanotubes capable of binding hydrophobic prosthetic groups such as hemin to facilitate hydrolase peroxidase cascade reaction. In addition, these nanotubes are shown to foreshadow the advanced trait of modern enzymes i.e., intermediate channelling. Chapter 3 demonstrates cross β amyloid enzyme nanohybrids that can foster extended sets of cascade reactions, starting from simple two-step, to multistep, to complex convergent cascades. Further, an intricate digital design with the help of three concatenated AND gates has been manifested to highlight the complexity of the overall systems. Chapter 4 presents the simultaneous generation of the fluorescence signal and motility by cross β amyloid-based, leading to the construction of fluorescent microswimmers via the facilitation of a complex divergent cascade network. Chapter 5 features the capabilities of short peptide-based amyloid assemblies to colocalize substrates and cofactors based on hydrophobic and coulombic effects to template a water mediated reduction reaction which is otherwise not feasible in absence of the amyloid. Chapter 6 demonstrates short peptide and nucleotide-based dynamic coacervates that can confine cytochrome c and temporally modulate a redox reaction catalyzed by the entrapped protein. Chapter 7 presents an overall summary of the work and describes the significant findings of these studies. In addition, a broad overview of the possible future directions has been discussed.

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