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dc.contributor.authorChitayat, Sethen
dc.date2007-09-27 11:46:38.753
dc.date.accessioned2007-09-28T18:03:20Z
dc.date.available2007-09-28T18:03:20Z
dc.date.issued2007-09-28T18:03:20Z
dc.identifier.urihttp://hdl.handle.net/1974/727
dc.descriptionThesis (Ph.D, Biochemistry) -- Queen's University, 2007-09-27 11:46:38.753en
dc.description.abstractProteins modularity enhances the multi-functionality and versatility of proteins by providing such properties as multiple and various ligand-binding sites, increased ligand affinity through the avidity effect, and the juxtaposition of ligand-binding modules near catalytic domains. An NMR-based "dissect-and-build" approach to studying modular protein structure and function has proven very successful, whereby modules are initially characterized individually and then correlated with the overall function of a protein. We have used the dissect-and-build approach and NMR to study two modular protein systems. Chapter 2 details the NMR solution structure of the weak-lysine-binding kringle IV type 8 (KIV8) module from the apolipoprotein(a) (apo(a)) component of lipoprotein(a) was determined and its ligand-binding properties assessed. In vitro studies have demonstrated the importance of the apo(a) KIV7 and KIV8 modules in mediating specific lysine-dependent interactions with the apolipoproteinB-100 (apoB-100) component of LDL in the initial non-covalent step of lipoprotein assembly. Notable differences identified in the lysine binding site (LBS) of the KIV8 were deemed responsible for the differential modes of apoB-100 recognition by KIV7 and KIV8. In addition, the KIV8 structure has brought to light the importance of an RGD sequence at the N-terminus of the apo(a) KIV8 module, which may mediate important apo(a)-integrin interactions. In Chapters 3-6, structure-function studies of the CpGH84C X82 and the CpGH84A dockerin-containing modular pair were conducted to understand how the varying modularity unique to the C-terminal regions of the secreted multi-modular family 84 glycoside hydrolases influences the spreading of Clostridium perfringens. Identification of a CpGH84C cohesin module (X82), and the structural characterization of a dockerin-containing modular pair provides the first evidence for multi-enzyme complex formation mediated by non-cellulosomal cohesin-dockerin interactions. The formation of large hydrolytic enzyme complexes introduces a novel mechanism by which C. perfringens may enhance its role in pathogenesis.en
dc.format.extent11513526 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoengen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectNMR spectroscopyen
dc.subjectProtein structureen
dc.subjectProtein-ligand interactionsen
dc.subjectExtracellular proteinsen
dc.subjectClostridium perfringensen
dc.subjectApolipoproteinsen
dc.subjectLow density lipoproteinen
dc.subjectBacterial pathogensen
dc.subjectCardiovascular diseaseen
dc.subjectMolecular biologyen
dc.subjectBiochemistryen
dc.subjectModular proteinsen
dc.titleNMR and Biophysical Studies of Modular Protein Structure and Functionen
dc.typethesisen
dc.description.degreePhDen
dc.contributor.supervisorSmith, Steven P.en
dc.contributor.departmentBiochemistryen
dc.degree.grantorQueen's University at Kingstonen


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