The objective of this study is to evaluate pseudo-substrates of pantothenate kinase (PanK) for the therapeutic treatment of multidrug resistant bacterial infections of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Pantothenate (Pan) analogs, including N- pentylpantothenamide (N5-Pan) and N-heptylpantothenamide (N7-Pan), hamper bacterial growth by utilizing the PanK enzymes, which normally catalyze the rate determining step of the Coenzyme A biosynthetic pathway. Here we report the structures of SaPanK, Human PanK3 and EcPanK complexed with N7-Pan or N5-Pan, all of which have provided the opportunity to investigate the structural differences of bacterial and human Pan binding sites. The MTT assay showed these analogs to exhibit no apparent cytotoxicity against Human A549 lung adenocarcinoma cells, human HepG2 hepatoma cells and human umbilical vein endothelial cells (HUVEC). The presented structural differences have the potential for aiding the development of species-specific antimicrobial compounds with minimal effects on human cells.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/35129 |
| Date | 18 March 2013 |
| Creators | Mottaghi, Katayoun |
| Contributors | Park, Hee-Won, Grant, Denis M. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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