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Inhibition of Membrane-Bound lytic Transglycosylase F (MltF) by Inhibitors of Lysozyme

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Title: Inhibition of Membrane-Bound lytic Transglycosylase F (MltF) by Inhibitors of Lysozyme
Author: Holland, Kathryn
Department: Department of Molecular and Cellular Biology
Program: Molecular and Cellular Biology
Advisor: Clarke, Anthony
Abstract: Peptidoglycan (PG) is an essential component of bacterial cells. PG forms a mesh-like sacculus surrounding the cell and is constantly being remodelled by a class of enzymes, known as lytic transglycosylases (LTs). Due to their integral role in PG metabolism LTs present an ideal target for antibiotics. However, the characterization of these enzymes is hindered by the insolubility and heterogeneity of their substrate. To address this issue the development a protocol for the preparation of a defined, homogenous substrate through the polymerization of Lipid II began. Preliminary results identified difficulties involved in producing this homopolymer but success in preparation of a homogenous, defined PG-based substrate was achieved. Also, the potential of the proteinaceous inhibitors, Ivy (inhibitor of vertebrate lysozyme) to serve as inhibitors of MltF was investigated. The trials completed provided data to support the hypothesis that Ivy’s normal physiological function is to control the activity of LTs.
Date: 2014-03
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