The caspase family of proteins is critical to biological understanding, because they serve as the final arbiters of life and death, being the initiators and executioners of cell death. Specifically, caspase-7 plays a key role in apoptosis, however its full complement of targets within the cell has not yet been elucidated, nor has its function been targeted by drug design efforts. These factors stem from the lack of fundamental understanding of the structural dynamics of the protein, including the mobile loops that constitute the active site binding groove of caspase-7, and their ability to modulate the function of the protein. In this work, we describe the importance of the entire loop bundle for catalysis, demonstrate a novel approach for allosteric control using loop movement, develop computational methods to engineer a new binding site for an allosteric effector and discover a hereunto unseen native disulfide within caspase-7 that may contribute to specificity and catalysis. The information obtained within this study is applicable for not only the study of caspase-7, but also the greater field of apoptosis research.
| Identifer | oai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:open_access_dissertations-1421 |
| Date | 13 May 2011 |
| Creators | Witkowski, Witold Andrej |
| Publisher | ScholarWorks@UMass Amherst |
| Source Sets | University of Massachusetts, Amherst |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Open Access Dissertations |
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