Tjoa, Stanley Evander Emeltan Vianney, Yoanes Maria Putra, Sulistyo Emantoko Dwi <i>In silico</i> mutagenesis: decreasing the immunogenicity of botulinum toxin type A <p>Botulinum toxin serotype A is a prominent therapeutic enzyme, for both clinical and cosmetic uses. Since this protein is produced by bacteria, it exhibits an allergenic effect when subjected to human therapy. Protein mutagenesis is one method to improve the characteristics of protein. However, <i>in silico</i> study is needed to give suggestion of which amino acid should be mutated. Hence, a lot of money and time can be saved. This study initially screened which residue of the Botulinum toxin serotype A is B-cell epitopes both linearly and conformationally. By overlapping the B-cell epitopes with the excluded conserve sequence, seven residues were allowed to be mutated. There were two proposed muteins showing a reduction in the antigenicity probability: Δ<i>E</i>147, E510F, T1062F, Δ<i>E</i>1080, N1089M and Δ<i>Q</i>1090; and <i>ΔE147</i>, E510F, T1062F, E1080W, N1089M and Δ<i>Q</i>1090. Molecular dynamics simulation of the 3D proposed muteins indicated an increase of flexibility in both muteins compared to that in the native protein. Both muteins have lower antigenicity. In addition, they are similar in structure, stability and functionality compared to the native protein.</p> Bioinformatics;botulinum toxin type A;B-cell epitopes prediction;immunogenicity;in silico mutagenesis 2019-01-16
    https://tandf.figshare.com/articles/journal_contribution/_i_In_silico_i_mutagenesis_decreasing_the_immunogenicity_of_botulinum_toxin_type_A/7593890
10.6084/m9.figshare.7593890.v1