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Abstract
Proteins are one class of biologically essential macromolecules and function in virtually every cellular process. Understanding of the functions and mechanisms of proteins not only is the essential and important part of basic science research, but also provides valuable insights into translational studies. The past several decades have witnessed a number of successes of proteins for drug discovery and development, in which proteins act either as drugs or as drug targets. Importantly, recent exponentially available genome sequence data has presented a rich but less-explored source of proteins, offering tremendous opportunities for basic and translational research.
The overall objective of my graduate studies is to characterize the functions of less-studied proteins using a set of interdisciplinary approaches and then explore their potential applications in drug discovery and development. Specially, my research focuses on the biochemical, functional, and structural investigation of two mushroom proteins and one bacterial protein. In this dissertation, Chapter 1 briefly introduces the cutting-edge strategies in exploring the potential of proteins as drug targets. Chapter 2 is on one glycan binding protein (GBP), named Y3, from the edible mushroom Coprinus comatus. We characterized its biochemical and structural properties, identified its glycan binding specificity, and uncovered its potent cytotoxicity along with the cellular mechanism in human Jurkat cells. Chapter 3 presents the characterization of one Y3 homolog, Ab-Y3, which originates from the editable mushroom Agaricus bisporus (white mushroom). We determined its biochemical and structural properties and identified its unique glycan binding profiles. Chapter 4 focuses on the dihydroxy-acid dehydratase from the cyanobacterium Synechocystis PCC 6803 (SnDHAD) that is essential to the biosynthesis of branched-chain amino acids. We reported its biochemical and structural properties. Importantly, our study suggested the promising application of DHAD as an antimicrobial target. Chapter 5 summarizes my graduate studies and envisions future work.
Overall, these results present an interdisciplinary pipeline for the functional characterization of less-explored proteins abundant in genome database, aiding the future development of novel drugs.
