http://hdl.handle.net/10033/6858 Wissenschaftlicher Direktor (GFW) Thu, 20 Jun 2013 03:27:24 GMT 2013-06-20T03:27:24Z http://hdl.handle.net/10033/293024 Title: Molecular dynamics reveal binding mode of glutathionylspermidine by trypanothione synthetase. Authors: Koch, Oliver; Cappel, Daniel; Nocker, Monika; Jäger, Timo; Flohé, Leopold; Sotriffer, Christoph A; Selzer, Paul M Abstract: The trypanothione synthetase (TryS) catalyses the two-step biosynthesis of trypanothione from spermidine and glutathione and is an attractive new drug target for the development of trypanocidal and antileishmanial drugs, especially since the structural information of TryS from Leishmania major has become available. Unfortunately, the TryS structure was solved without any of the substrates and lacks loop regions that are mechanistically important. This contribution describes docking and molecular dynamics simulations that led to further insights into trypanothione biosynthesis and, in particular, explains the binding modes of substrates for the second catalytic step. The structural model essentially confirm previously proposed binding sites for glutathione, ATP and two Mg(2+) ions, which appear identical for both catalytic steps. The analysis of an unsolved loop region near the proposed spermidine binding site revealed a new pocket that was demonstrated to bind glutathionylspermidine in an inverted orientation. For the second step of trypanothione synthesis glutathionylspermidine is bound in a way that preferentially allows N(1)-glutathionylation of N(8)-glutathionylspermidine, classifying N(8)-glutathionylspermidine as the favoured substrate. By inhibitor docking, the binding site for N(8)-glutathionylspermidine was characterised as druggable. Tue, 01 Jan 2013 00:00:00 GMT http://hdl.handle.net/10033/293024 2013-01-01T00:00:00Z http://hdl.handle.net/10033/25175 Title: From mouse genetics to systems biology. Authors: Balling, Rudi Sun, 01 Jul 2007 00:00:00 GMT http://hdl.handle.net/10033/25175 2007-07-01T00:00:00Z http://hdl.handle.net/10033/16972 Title: Phagocytosis assay based on living Candida albicans for the detection of effects of chemicals on macrophage function Authors: Klippel, Nina; Bilitewski, Ursula Sun, 07 Jan 2007 00:00:00 GMT http://hdl.handle.net/10033/16972 2007-01-07T00:00:00Z http://hdl.handle.net/10033/13021 Title: Biochemische Methoden in der Wasseranalytik - Stand der Technik und Perspektiven - Teil II: Organismische Tests Authors: Bilitewski, Ursula Tue, 31 Jul 2007 08:58:27 GMT http://hdl.handle.net/10033/13021 2007-07-31T08:58:27Z