In this video from PASC16, Annick V. Renevey from ETH Zurich describes her poster: The Importance of N-Methylations for the Stability of the β6.3-Helical Conformation of Polytheonamide B.
“Polytheonamide B (PTB) is a highly cytotoxic transmembrane cation channel consisting of 49 residues, of which more than half are posttranslationally modified. Epimerizations result in alternating L- and D- amino acids allowing the peptide to adopt a β-helical structure stable in solution. The role of the other posttranslational modifications (PTMs): hydroxylations, side chain C-methylations and side chain N-methylations, is less understood. The importance of these PTMs for the β6.3-helical structure is investigated using molecular dynamics simulations. Groups or individual modified residues are reverted to their precursor amino acids and the conformational effect on PTB monitored. The simulation results indicate that the N-methylations are crucial for the stability of the β6.3-helix due to the formation of the side chain?side chain hydrogen bond chains that act like an “exoskeleton” for the helix. With unmethylated asparagine residues, the H-bond chains are unstable in polar solvents, resulting in the loss of the helical structure.”
Thanks to Rich Brueckner from insideHPC Media Publications for recording the video.
For the full list of the PASC16 video please visit the PASC16 Video Gallery.