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Novel Insights in Structure and Mechanism of Escherichia coli Transketolase

dc.contributor.advisorTittmann, Kai Prof. Dr.
dc.contributor.authorRabe von Pappenheim, Fabian
dc.date.accessioned2018-05-18T08:10:33Z
dc.date.available2018-05-18T08:10:33Z
dc.date.issued2018-05-18
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-002E-E3EE-6
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-6876
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc570de
dc.titleNovel Insights in Structure and Mechanism of Escherichia coli Transketolasede
dc.typedoctoralThesisde
dc.contributor.refereeFicner, Ralf Prof. Dr.
dc.date.examination2017-05-23
dc.description.abstractengThiamine diphosphate (ThDP) dependent enzymes fulfill a number of indispensable functions in metabolism. Further, they are well-researched work-horses of biotechnology. Thus, deepening of our mechanistic and structural knowledge of these is imperative in improving biotechnological approaches, gain fundamental insight in enzymological principles and possibly develop antibiotics. In this work we present fundamental insights in multiple mechanistic aspects of ThDP-dependent enzymes using the Escherichia coli transketolase as model system. Studies on the control of cofactor dynamics and their impact on catalysis provided a model by which intrinsic cofactor movement facilitates bond strain reducing the energy barrier for C-C bond cleavage. Further, a core tenet of ThDP-facilitated catalysis was challenged by generating a non-aromatic, electrophilic keto-intermediate in a transferase by mutagenesis of a single, intermediate-stabilizing residue. The role of conserved features of transketolases in controlling cofactor properties was gauged. The mode of action of the naturally occurring antibiotic 2’-methoxy thiamine diphosphate was investigated and a model based on enzyme-selective disturbance of the cofactor activation, supported by ultra-high resolution crystallographic data and NMR data, was derived.de
dc.contributor.coRefereeKonrad, Manfred Dr.
dc.subject.engEnzymologyde
dc.subject.engThiamine Diphosphatede
dc.subject.engCarbohydratesde
dc.subject.engEnzyme Dynamicsde
dc.identifier.urnurn:nbn:de:gbv:7-11858/00-1735-0000-002E-E3EE-6-4
dc.affiliation.instituteBiologische Fakultät für Biologie und Psychologiede
dc.subject.gokfullBiologie (PPN619462639)de
dc.identifier.ppn1022548220


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