EMAN RESEARCH PUBLISHING | Journal | <p><em>In silico</em> Studies of Parasporin Proteins: Structural and Functional Insights and Proposed Cancer Cell Killing Mechanism for Parasporin 5 and 6</p>
Microbial and anti-microbial compound biology
RESEARCH ARTICLE   (Open Access)

In silico Studies of Parasporin Proteins: Structural and Functional Insights and Proposed Cancer Cell Killing Mechanism for Parasporin 5 and 6

Nasima Aktar1,2, Muhammad Manjurul Karim1, Shakila Nargis Khan1, Mustafizur Rahman3, Anowara Begum1, Md. Mozammel Hoq1,*

+ Author Affiliations

Microbial Bioactives 2(1) 082-090 https://doi.org/10.25163/microbbioacts.21007A0621280219

Submitted: 06 April 2018  Revised: 08 February 2019  Published: 28 February 2019 

Significance: Structural and functional insights of anti-cancer proteins from Bacillus thuringiensis.

Edited by: El-Sayed A. El-Sheikh, PhD . Plant Protection Department, Faculty of Agriculture, Zagazig University, Zagazig, Egypt.

Abstract


Background: Cancer is the leading cause of death in the world and the new types of cancer are diagnosed regularly but the advancement in their treatment is relatively slow and not to mention very costly. Parasporins (PS), parasporal inclusion proteins from Bacillus thuringiensis, possess specific cytotoxicity against different cancer cells which has suggested them to be potential for cancer treatment due to their specific binding to cancer cells. Methods: Computational investigation were performed to exploit their physicochemical characteristics, structural properties including three dimensional (3D) model, model quality analysis, phylogenetic assessment and functional analysis along with the cancer-cell killing mechanism of PS-5 and PS-6 proteins using standard tools of bioinformatics. Results: PS proteins were found to be slightly acidic based on their isoelectric points i.e., pI ranging from 5.12- 6.19, and the instability indices (29.03- 42.31) indicate their highly stable nature in test tubes and higher aliphatic indices (62.54-94.75) indicate their thermostability, a feature suitable for high-level industrial production. In silico analysis of cellular localization predicts that the parasporins are mostly located in the cytoplasm and few in the plasma membrane but devoid of any signal peptide. The generated 3D models of PS proteins upon verification by Ramachandran plot analysis confirmed that our prediction lies in the good quality model range and facilitated the understanding of the very protein folding, assembly into complexes and cell killing mechanisms. It could be hypothesized that the PS-5 protein might induce apoptosis or act as β- pore forming toxin to kill specific cancer cells while PS-6 might act simply as pore forming toxin. Conclusion: The theoretical overview of this research would facilitate the researchers with valuable insights of the PS protein structures, cancer cell killing mechanism of PS-5 and PS-6 proteins eventually in tumor micro-environment and their receptor molecules with a view to develop anti-cancer drugs.

Keywords: Parasporin, Domain, Motif, Cytotoxicity, Molecular docking.

Significance: Structural and functional insights of anti-cancer proteins from Bacillus thuringiensis.

Edited by: El-Sayed A. El-Sheikh, PhD

Plant Protection Department, Faculty of Agriculture, Zagazig University, Zagazig, Egypt.

Abbreviations: Bt, Bacillus thuringiensis; PS, Parasporin; β-PFT, β- Pore Forming Toxin; CD, Circular Dichroism; Cry, Crystal; pI, Isoelectric point; AI, Aliphatic Index; GRAVY, Grand average of hydropathy; PI, Phosphatidyl Inositol; GPI, Glycosyl Phosphatidyl Inositol; GOL, Glycerol; 13D, 1, 3- Diaminopropane; Br, Bromide; NGA, N- Acetyle- D- Galactosamine; U1, Uracil; E64, N- [N- [1- Hydroxycarboxyethyl- Carbonyl] Leucylamino- Butyl]- Guanidine; HEA, Hydroxyethylamine; MN, Manganese (II) ion.

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