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dc.contributor.authorScott, Richard Kennedy-
dc.descriptionPhD Thesisen_US
dc.description.abstractPart one covers an investigation into the secondary and tertiary structure of the protein Xylanase found in Pseudomonasfluorescens subspecies cellulosa. Part two documents the Computer Aided Design of Novel Quinazoline Antifolates for the enzyme Thyrnidylate Synthase. Partone Mature Xylanase protein consists of two distinct regions - a cellulose binding domain and a catalytic region, A and B respectively. Computer modelling of tertiary structure from primary sequence and secondary turn information proved difficult in the absence of experimental X-ray crystal data. Consequently,a series of modified proteins bbased on the Xylanase were prepared by Recombinant DNA technology for extraction and purification. The modified proteins were to be used as a bench mark for quantitative and definitive calculation and detennination of the secondary structure of the xylanase. This was to provide an excellent reference point for theoretical modelling of tertiary structure. Part one of the Thesis documents Computer Modelling work and protein purification and extraction of the xylanase. Part two Thymidylate Synthase (TS) exists as dimer with a single active site in each subunit. It has been crystallised in two forms; a "reduced" (major), and "oxidised" (minor) form. The major form of TS contains dUMP covalently bound to cysteine in both active sites and in the presence of CB3717. One active site of the minor form contains dUMP non-covalently bound and in the presence of CB3717 while the other active site contains only inorganic phosphate and CB3717. The active site of TS is a large cavity that binds CB3717 into two possible confirmations. One is seen in the major form and one in the minor form. Part two of my research documents an investigation into enzyme/inhibitor interaction in TS and covers the Computer Aided Design of a series of inhibitors based on the knowledge of the TS active site. Several of these compounds have been put forward as target compounds for synthesis.en_US
dc.publisherNewcastle Universityen_US
dc.titleProtein modelling and associated drug designen_US
Appears in Collections:School of Chemistry

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