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Structure, Function, and Inhibition of Peptidoglycan O-Acetyltransferase A from Staphylococcus aureus

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dc.contributor.advisor Clarke, Anthony J. Jones, Carys S. 2020-05-19T17:55:10Z 2020-05 2020-04-21 2020-05-19
dc.description.abstract Peptidoglycan (PG) is an essential cell wall component of most bacteria and serves to resist turgor pressure and protect the cell. Many bacteria modify their PG layer post-biosynthetically, which can have implications on pathogenicity. O-Acetylation of PG is an important modification utilized by both Gram-positive and Gram-negative bacteria to regulate autolysins and provide resistance to host-immune attack by lysozyme. This modification commonly occurs in several notable pathogens, including Staphylococcus aureus. In Gram-positive bacteria, PG O-acetylation is accomplished by a single dual domain enzyme, O acetyltransferase A (OatA). As a recognized virulence factor, OatA is of interest in the development of novel strategies to overcome antimicrobial resistance. In this study, S. aureus OatA was subjected to a large high-throughput screen to identify and characterize inhibitors of the enzyme. To improve our understanding of the PG O-acetylation system as a whole, the structures and functions of both domains of S. aureus OatA were also investigated. The topology of the N-terminal transmembrane domain was determined, and putative functional residues were investigated with in vivo and in vitro mutagenesis studies. A model for its mechanism and interaction with the C-terminal domain is proposed. Furthermore, the crystal structure of the C-terminal domain of S. aureus OatA is presented alongside an analysis of its catalytic mechanism. en_US
dc.language.iso en en_US
dc.rights Attribution-NoDerivatives 4.0 International *
dc.rights.uri *
dc.subject microbiology en_US
dc.subject peptidoglycan en_US
dc.subject O-acetyltransferase A en_US
dc.subject Staphylococcus aureus en_US
dc.subject biochemistry en_US
dc.title Structure, Function, and Inhibition of Peptidoglycan O-Acetyltransferase A from Staphylococcus aureus en_US
dc.type Thesis en_US Molecular and Cellular Biology en_US Doctor of Philosophy en_US Department of Molecular and Cellular Biology en_US
dc.description.embargo 2021-04-20
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