Journal article
Effect of oxidation and mutation on the conformational dynamics and fibril assembly of amyloidogenic peptides derived from apolipoprotein C-II
FS Legge, KJ Binger, MDW Griffin, GJ Howlett, D Scanlon, H Treutlein, I Yarovsky
Journal of Physical Chemistry B | AMER CHEMICAL SOC | Published : 2009
DOI: 10.1021/jp903842u
Abstract
The oxidation of methionine residues in proteins can inhibit the self-assembly of proteins to form amyloid fibrils. For human apolipoprotein (apo) C-II the oxidation of methionine at position 60 inhibits fibril formation by the mature protein and by the core peptides apoC-II56-76 and apoC-IL60-70. To investigate the molecular nature of these effects, we carried out fully solvated, all-atom molecular dynamics simulations of the structural changes in apoC-II56-76 associated with substitutions of oxidized methionine (Met ox) at position 60. The results with apoC-II 56-76 (Met ox) showed less flexibility in structure, leading to a perturbation of the hydrophobic core. Valine substitution at posi..
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Awarded by ARC
Awarded by Australian Research Council
Funding Acknowledgements
The authors acknowledge the ARC (Australian Research Council) grant no. LP0562041 and Cytopia Ply. Ltd. for providing funding for this project, and to APAC (Australian Partnership for Advanced Computing) for providing a grant of computer time. We also acknowledge colleagues in our group, Andrew Hung and Nevena Todorova.