ELUCIDATING THE MOLECULAR BASIS OF INHIBITION OF ENZYMES ESSENTIAL FOR BATERIALVIRULENCE: THE ACTIVITY OF THREE GLYCOSYLTRANSFERASES AND A POTENTIAL DRUG TARGET, UNDECAPRENYL PYROPHOSPHATE SYNTHASE

1 online resource (84 pages) : PDF

2016

University of North Carolina at Charlotte

The fight against bacterial infection is one of the most important branches of modern medicine. Due to the emergence of strains of antibiotic-resistant bacteria, researchers have been presented with complex challenges in an effort to combat these stronger bacteria that pose a significant threat to our health. Bacteria possess certain distinct features that protect them from the outside environment, such as their cell wall, and, in the case of Gram-negative bacteria, the outer membrane layer of their cell envelope. The cell wall is absolutely essential for bacterial survival, such that removal or an alteration in any of its components, results in the death of bacteria. Thus, many research projects aim to tackle pathways leading to formation of the polysaccharide cell wall. In this work, we study the activity and inhibition of four proteins which contribute to bacterial virulence. The first two proteins, LgmA and LgmC, are thought to be part of the pathway that modifies Lipid A, a component of the outer membrane, in Bordetella pertussis. Both enzymes are studied alongside WecA, a well-known, already characterized hexosyltransferase from E. coli, to explore differences in activity and inhibition of different classes of glycosyltransferases. Lastly, we conduct structural and computational studies of undecaprenyl pyrophosphate synthase (UPPS), a protein that is indispensable for cell wall biosynthesis. Our results provide some insight into the functionality and inhibition of each enzyme, and consequently, may contribute to the improvement or design of novel inhibitors of bacterial enzymatic activity.

masters theses

Chemistry
Biology
Biochemistry

M.S.

Glycosyltansferase
Lgma
Lipid A
Tunicamycin
UPPS
WecA

Chemistry

Troutman, Jerry

Afonin, Kirill
Jacobs, Donald
Vivero-Escoto, Juan

Thesis (M.S.)--University of North Carolina at Charlotte, 2016.

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Okwei_uncc_0694N_11166

http://hdl.handle.net/20.500.13093/etd:1541