Die Röntgenstrukturen der Glutamatdehydrogenase von Plasmodium falciparum und der Liponamiddehydrogenase von Trypanosoma cruzi. Zielmoleküle für das strukturbasierte Design neuer antiparasitärer Wirkstoffe

In der vorliegenden Arbeit wurden die Kristallstrukturen der Glutamatdehydrogenase des Malariaerregers Plasmodium falciparum und der Liponamiddehydrogenase von Trypanosoma cruzi, dem Erreger der Chagas-Krankheit, aufgeklärt. Beide Enzyme sind validierte bzw. mögliche Zielmoleküle für das rationale D...

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Bibliographic Details
Main Author: Werner, Christof
Contributors: Klebe, Gerhard (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Published: Philipps-Universität Marburg 2008
Pharmazeutische Chemie
Online Access:PDF Full Text
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Table of Contents: In the work presented, the crystal structures of Plasmodium falciparum glutamate dehydrogenase (GDH) and of Trypanosoma cruzi Lipoamide dehydrogenase (LipDH) were determined to a resolution of 2.7 and 1.9 Angstroms, respectively. Both are targets for the design of novel antiparasitic drugs, because they are involved in the parasites defense against oxidative stress or in the production of reactive oxygen species (in the case of lipoamide dehydrogenase). The work also deals with the similarities and differences of the two parasite enzymes compared to closely related proteins and the respective proteins of the human host. The results provide a starting point for further studies with the aim to find selective inhibitors of P. falciparum GDH and improved so-called subversive substrates of T. cruzi LipDH with methods of structure-based drug design.