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DC Field | Value | Language |
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dc.contributor.advisor | Berti, Paul | - |
dc.contributor.author | Lou, Meiyan | - |
dc.date.accessioned | 2017-06-14T13:05:32Z | - |
dc.date.available | 2017-06-14T13:05:32Z | - |
dc.date.issued | 2008-09 | - |
dc.identifier.uri | http://hdl.handle.net/11375/21606 | - |
dc.description.abstract | AroA catalyzes the sixth step of the shikimate biosynthetic pathway which produces aromatiG amino acids in plants and bacteria, but is absent in mammals. This makes AroA an attractive antimicrobial target. The transition state (TS) structures of AroA- and acid-catalyzed 5-eno/pyruvyl shikimate-3-phosphate (EPSP) hydrolysis were studied in atomic detail by kinetic isotope effect (KIE) measurement. Enzymes bind their transition states more tightly than any other species, so molecules that closely resemble the transition state would have a high affinity for the enzyme and be good inhibitors. Radiolabelled EPSPs were synthesized and a KIE measurement method was developed. Six KIEs were measured for both the AroA- and acid-catalyzed reactions. KIEs for the AroA reaction indicate a cationic TS structure. The acid-catalyzed reaction may employ a slightly different mechanism with an earlier TS. A computational TS model was found and its KIEs were calculated. It demonstrated good agreement with the experimental values at most positions. The model is being modified to improve the agreement with the experimental KIEs. This TS structure will be a good starting point for inhibitor design. All these efforts, hopefully, can make a positive contribution to the development of antimicrobial drugs. | en_US |
dc.language.iso | en | en_US |
dc.subject | Transition State | en_US |
dc.subject | State Analysis | en_US |
dc.subject | AroA Reaction | en_US |
dc.subject | Kinetic Isotope | en_US |
dc.title | Transition State Analysis of the AroA Reaction Using Kinetic Isotope Effects | en_US |
dc.contributor.department | Biochemistry and Biomedical Sciences | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
Appears in Collections: | Digitized Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Lou_Meiyan_2008Sept_Masters.pdf | 4.9 MB | Adobe PDF | View/Open |
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