Reducing the Immunogenicity of Pulchellin A-Chain, Ribosome-Inactivating Protein Type 2, by Computational Protein Engineering for Potential New Immunotoxins
نویسندگان
چکیده
Pulchellin is a plant biotoxin categorized as type 2 ribosome-inactivating protein (RIPs) which potentially kills cells at very low concentrations. Biotoxins serve targeting immunotoxins (IT), consisting of antibodies conjugated to toxins. ITs have two independent components, human antibody and toxin with bacterial or source; therefore, they pose unique setbacks in immunogenicity. To overcome this issue, the engineering epitopes one beneficial methods elicit an immunological response. Here, we predicted tertiary structure pulchellin A-chain (PAC) using five common powerful servers adopted best model after refining. Then, four distinct computational approaches identified conformational B-cell epitopes. This approach some amino acids potential for lowering immunogenicity by point mutation. All mutations were then applied generate containing all (so-called PAM). Mutants’ was assessed compared wild well other mutant characteristics, including stability compactness, computationally examined addition The findings revealed reduction mutants significantly N146V R149A. Furthermore, demonstrated remarkable validity Molecular Dynamic (MD) simulations. During docking simulations, most homologous pulchellin, Abrin-A control. In addition, candidate (PAM) disclosed high level stability, making it experimental deployment. conclusion, eliminating epitopes, our provides less immunogenic IT based on PAC.
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ژورنال
عنوان ژورنال: J
سال: 2023
ISSN: ['2571-8800']
DOI: https://doi.org/10.3390/j6010006