dc.contributor.author | Kuehm, Oliver | |
dc.date.accessioned | 2020-12-16T12:53:55Z | |
dc.date.available | 2020-12-16T12:53:55Z | |
dc.date.issued | 2020-12-16T12:53:55Z | |
dc.identifier.uri | http://hdl.handle.net/10222/80105 | |
dc.description.abstract | Enzymes of the enolase superfamily (ENS) of share a high level of structural similarity and catalyze a conserved partial reaction yet display an overall mechanistic divergence. Mandelate racemase (MR) serves as a paradigm for the enzyme-catalyzed abstraction of an a-proton from a carbon acid substrate. This work described the characterization of a series of potent chloro- and fluoro-substituted phenylboronic acid (PBA) inhibitors of MR, including 3,4-dichloroPBA, for which MR exhibited the highest binding affinity observed to-date (Kd = 13.8 nM). Investigations on the conserved KxK motif of the MR subgroup, revealed that the KxK residue was essential for catalysis and for the stability of MR and L-tartrate dehydratase. The K164M and K164R MR variants displayed a change in thermal melting temperature (∆Tm) of –4.03 and –8.36 °C, respectively. Finally, approaches towards production of human reverse thymidylate synthase, an ENS enzyme, using precursor proteins bearing two protease specific sites were described. | en_US |
dc.language.iso | en | en_US |
dc.subject | Enolase | en_US |
dc.subject | Mandelate racemase | en_US |
dc.subject | Inhibition | en_US |
dc.subject | Thermal stability | en_US |
dc.subject | Reverse thymidylate synthase | en_US |
dc.title | Investigations on Enzymes of the Enolase Superfamily | en_US |
dc.type | Thesis | en_US |
dc.date.defence | 2020-12-07 | |
dc.contributor.department | Department of Biochemistry & Molecular Biology | en_US |
dc.contributor.degree | Master of Science | en_US |
dc.contributor.external-examiner | N/A | en_US |
dc.contributor.graduate-coordinator | Dr. Barbara Karten | en_US |
dc.contributor.thesis-reader | Dr. Catherine Too | en_US |
dc.contributor.thesis-reader | Dr. Jan Rainey | en_US |
dc.contributor.thesis-reader | Dr. Paul X-Q. Liu | en_US |
dc.contributor.thesis-supervisor | Dr. Stephen L. Bearne | en_US |
dc.contributor.ethics-approval | Not Applicable | en_US |
dc.contributor.manuscripts | Not Applicable | en_US |
dc.contributor.copyright-release | Not Applicable | en_US |