Characterization of prokaryotic pantothenate kinase enzymes and the development of type-specific inhibitors

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dc.contributor.advisorStrauss, Ericken_ZA
dc.contributor.authorKoekemoer, Lizbeen_ZA
dc.contributor.otherStellenbosch University. Faculty of Sciences. Dept. of Biochemistry.en_ZA
dc.date.accessioned2011-11-24T10:46:42Zen_ZA
dc.date.accessioned2011-12-06T08:36:47Z
dc.date.available2014-12-01T03:00:06Z
dc.date.issued2011-12en_ZA
dc.descriptionThesis (PhD)--Stellenbosch University, 2011.en_ZA
dc.description.abstractENGLISH ABSTRACT: Pantothenate kinase (PanK) enzymes catalyze the first reaction in the five step biosynthesis of the essential cofactor coenzyme A. Enzymes representing each of the three identified PanK types have been studied and characterized and these PanK types exhibits a unique diversity between different organisms, therefore highlighting them as potential drug targets. In this study the type III PanK of specifically pathogenic bacteria were characterized with the goal of developing type-specific inhibitors. Several questions about the activity of the Mycobacterium tuberculosis enzyme was answered, which addresses the contradicting results achieved in related PanK studies performed to date. Furthermore the first inhibitors, that are competitive to the pantothenate binding site, were designed, synthesized and tested against the Pseudomonas aeruginosa enzyme. This resulted in the discovery of the most potent inhibitors of the type III PanKs to date.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Pantoteensuurkinase-ensiem (PanK) kataliseer die eerste stap in die vyf stap biosintese van die lewens belangrike en essensiële kofaktor, koënsiem A (KoA). Die meerderheid patogeniese bakterieë, waaronder die organisme wat tuberkulose veroorsaak, besit ‘n unieke vorm van die PanK-ensiem. Gevolglik word hierdie ensieme as belangrike teikens vir die ontwikkeling van antibakteriële middels beskou. In hierdie studie is die aktiwiteit van die Mycobacterium tuberculosis ensiem gekarakteriseer wat verskeie teenstrydige bevindings oor hierdie ensiem beantwoord het. Verder is nuwe inhibitore vir die Pseudomonas aeruginosa ensiem ontwerp, gesintetiseer en getoets. Die beste inhibitore van hierdie tipe ensiem tot op hede is sodoende geïdentifiseer.en_ZA
dc.embargo.terms2014-12-01
dc.format.extentxxii, 121 pages : illustrations (some colour)en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/18099en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subjectCoenzyme A -- Biosynthesisen_ZA
dc.subjectPantothenate kinaseen_ZA
dc.subjectInhibitor developmenten_ZA
dc.subjectEnzymologyen_ZA
dc.subjectUCTDen_ZA
dc.titleCharacterization of prokaryotic pantothenate kinase enzymes and the development of type-specific inhibitorsen_ZA
dc.typeThesisen_ZA
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