In silico mutagenesis: decreasing the immunogenicity of botulinum toxin type A.

Tjoa, Stanley Evander Emeltan and Vianney, Yoanes Maria and Putra, Sulistyo Emantoko Dwi (2019) In silico mutagenesis: decreasing the immunogenicity of botulinum toxin type A. In silico mutagenesis: decreasing the immunogenicity of botulinum toxin type A., 37 (18). pp. 4767-4778. ISSN 16102940

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Abstract

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, in silico 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: ΔE147, E510F, T1062F, ΔE1080, N1089M and ΔQ1090; and ΔE147, E510F, T1062F, E1080W, N1089M and ΔQ1090. 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.

Item Type:	Article
Uncontrolled Keywords:	Bioinformatics; botulinumtoxin type A; B-cell epitopesprediction; immunogenicity;in silicomutagenesis
Subjects:	Q Science > Q Science (General)
Divisions:	Faculty of Technobiology > Department of Biology
Depositing User:	Sulistyo Emantoko 61116
Date Deposited:	16 Dec 2019 07:09
Last Modified:	09 Jun 2021 02:21
URI:	http://repository.ubaya.ac.id/id/eprint/36898

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