Date of Award
Ph.D. in Chemistry
Copper is one of the most abundant and less toxic metal on earth. In nature, a variety of proteins have copper in their active site structure. Copper bound to amyloid proteins are implicated to play pathophysiological roles in neurodegenerative diseases. On the other hand, copper containing metalloenzymes in Nature catalyze important biochemical reactions. Cu containing metalloenzymes play a significant role in a variety of functions viz. electron transfer, oxygen reduction, oxygen transport, and substrate oxidation owing to the readily available redox states of Cu+/Cu2+. While Cu bound to amyloid proteins that are often referred as intrinsically disordered or misfolded proteins have a disordered structure with multiple metal binding site, Cu containing metalloenzymes have a highly ordered specific structure around the metal center as well as around the periphery. The unique coordination environment around the metal center allows for highly specific biochemical reactions in ambient conditions that are otherwise difficult to perform in laboratory. Due to the lack of a specific structure in amyloid proteins, the reactions carried out by Cu bound amyloid beta are not selective or enzymatic. Hence overall, metalloenzymes display a rich diversity in the nature of Cu-active sites and subsequent reactivity. Inspired from Nature, the design of Artificial Metallozymes (ArMs) has emerged as an important goal. The ArMs mimic the first and second coordination sphere characteristics of a natural enzyme with the aim to develop a structural and functional model of an enzyme. This thesis discusses the importance of Cu proteins with relevance to neurodegenerative diseases as well as biocatalysts involved in small molecule activation and processing. The purpose of the thesis is to reiterate the wide array of Cu proteins in nature with diverse structure, reactivity, and implications towards human health and energy crisis.
Mitra, Suchitra, "EXPLORING COPPER ACTIVE SITES IN BIOLOGY WITH RELEVANCE TO ALZHEIMER'S DISEASE AND DE NOVO DESIGNED BIOCATALYSTS" (2021). Electronic Theses and Dissertations. 2163.
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