dc.creator | Alvin, Joseph William | |
dc.date.accessioned | 2020-08-22T20:38:24Z | |
dc.date.available | 2018-01-31 | |
dc.date.issued | 2017-08-04 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-07282017-083534 | |
dc.identifier.uri | http://hdl.handle.net/1803/13691 | |
dc.description.abstract | C. difficile is the leading cause of hospital-acquired diarrhea and pseudomembranous colitis worldwide. The major virulence factors in CDI (TcdA and TcdB) are members of the Large Clostridial Toxin (LCT) family. Due to the growing global healthcare burden of C. difficile, it remains the most-studied of the LCT-producing Clostridia. In an effort to further our understanding, I sought to study the structural characteristics of the TcdA/B-GTD using a combination of sequence comparison, structural modeling, crosslinking, and crystallography with substrates and inhibitors. Despite substitutions in the synthetic compound, the active site and sugar selection residues remained unchanged in both proteins compared to the native substrate. Overall, my work contributes to the study of LCT-GTDs by identifying promising methods for crosslinking and providing new structures of TcdA and TcdB-GTD using a non-hydrolyzable analog and the small molecule apigenin. In determining the five new structures of TcdA and TcdB-GTD we observed disparate conformations of the active site tryptophan. | |
dc.format.mimetype | application/pdf | |
dc.subject | Clostridium difficile | |
dc.subject | glucosyltransferase | |
dc.subject | large clostridial toxin | |
dc.title | Structure-Function Study of Large Clostridial Toxins and their
Glucosyltransferase Domains | |
dc.type | dissertation | |
dc.contributor.committeeMember | Tim Cover | |
dc.contributor.committeeMember | Nick Reiter | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Chemical and Physical Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2018-01-31 | |
local.embargo.lift | 2018-01-31 | |
dc.contributor.committeeChair | Al Beth | |