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What and Who

Structure based ligand design - a case study on the DNA-methyltransferase MTaqI

Prof. Dr. Axel Scheidig
Lehrstuhl für Biophysik, Universität des Saarlandes
Talk
AG 1, AG 2, AG 3, AG 4, AG 5  
MPI Audience

Date, Time and Location

Wednesday, 17 November 2004
17:00
-- Not specified --
46.1 - MPII
024
Saarbrücken

Abstract

In order to catalyze the transfer of the activated methyl group from the cofactor /S/-adenosyl-L-methionine to the 6-amino group of adenine within the double-stranded DNA sequence 5'-TCGA-3', the target nucleotide is flipped out of the DNA helix(1). Stabilization of the extrahelical conformation is achieved by a hitherto unre­cognized DNA compression perpendicular to the DNA helix axis and relocation of the partner base thymine in an interstrand pi-stacked position.


All this and in addition, the cata­lytic mechanism of N6-adenine DNA methyltransferases can be deduced from the complex structure of the enzyme with bound DNA. However, in order to get the ternary structure of the complex different cofactor analogues had to be tested. The logic behind the modifications of the cofactor analogues and the technical invention connected to this work will be presented.

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Ruth Schneppen-Christmann, 11/10/2004 08:50 -- Created document.