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Title: Mechanistic and structural studies of type I dehydroquinase
Author: McNae, Iain William
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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In fungi the central five steps of the shikimate pathway are fused into a single protein called the AROM enzyme. This has been shown to be related to the QUTA and QUTR proteins found in fungi which are responsible for the activation and repression of the transcription of enzymes found in the quinic acid utilisation pathway. The shikimate and quinate pathways therefore appear to be linked by a complex web of evolutionary relationships. Here research attempting to understand more fully the active mechanism of type I dehydroquinase from S. typhi is discussed. This research utilises molecular biological, biochemical and crystallographic techniques. Crystallographic trials of the dehydroquinase like domain of QUTR from A. Nidulans are also discussed. After literature review in chapter 1 and explanation of experimental techniques used in chapter 2, chapter 3 describes the production of active site mutants of type I dehydroquinase from S. typhi. These mutants are shown to decrease enzyme activity. In chapter 4 crystallisation of type I dehydroquinanse and its subsequent diffraction is described and discussed. Chapter 5 describes and discusses five different forms of wild type I dehydroquinase from S. typhi. In chapter 6 mutant crystal structures are described and discussed. In chapter 7 kinetic studies of putative dehydroquinase inhibitors are described and discussed. The crystal structure of one of these inhibitors is also described. In chapter 8 crystallisation trials of the dehydroquinase like domain of the QutR protein are discussed. In chapter 9 all results are discussed including the unusual packing of type I dehydroquinase from S. typhi and the implications of results to explaining the enzymes reaction mechanism. A reaction mechanism for type I dehydroquinase is proposed. In appendix 1 the structural solution and refinement of cytochrome C4 from Pseudomonas aeruginosa is described and compared to a previously solved cytochrome C4 from Pseudomonas stutzeri.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available