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Subcloning, Enzymatic Characterization, and in silico Docking of Transglutaminase 2

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Title Subcloning, Enzymatic Characterization, and in silico Docking of Transglutaminase 2
Author: Fisher, Oriana
Abstract: Tissue transglutaminase (TGaseII) is an enzyme that is implicated in a wide range of diseases, and catalyzes the formation of γ-glutamyl-ε-lysine crosslinks. While other related enzymes have been extensively characterized, much remains unknown about TGaseII. Our goal is to find inhibitors of TGaseII using a guided approach. In order to do this, three separate constructs of the human form of the enzyme were expressed and purified in E. coli with the intention of co-crystallizing the enzyme bound to an inhibitor and solving its structure. Additionally, the results of two previous structural studies of the human form of the enzyme were used for in silico docking to identify small molecules with which it might interact, as well as to help determine how two known inhibitors interact with TGaseII. The three constructs studied had drastically different levels of enzymatic activity and degrees of purity. This seems to further elucidate the structural mechanisms of the enzyme. The docking experiments identified a loop region of the protein with which several ligands and inhibitors associated. The compounds identified in the docking experiments will be evaluated in a cell-based assay in Dr. Rajiv Ratan’s lab at Cornell University.
URI: http://hdl.handle.net/10192/23253
Date: 2009-05-15

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