Repository of Research and Investigative Information

Repository of Research and Investigative Information

Dezful University of Medical Sciences

Structural pierce into molecular mechanism underlying Clostridium perfringens Epsilon toxin function

(2017) Structural pierce into molecular mechanism underlying Clostridium perfringens Epsilon toxin function. Toxicon. pp. 90-99. ISSN 0041-0101

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Abstract

Epsilon toxin of the Clostridium perfringens garnered a lot of attention due to its potential for toxicity in humans, extreme potency for cytotoxicity in mice and lack of any approved therapeutics prescribed for human. However, the intricacies of the Epsilon toxin action mechanism are yet to be understood. In this regard, various in silico tools have been exploited to model and refine the 3D structure of the toxin and its two receptors. The receptor proteins were embedded into designed lipid membranes within an aqueous and ionized environment. Thereafter, the modeled structures subjected to series of consecutive molecular dynamics runs to achieve the most natural like coordination for each model. Ultimately, protein-protein interaction analyses were performed to understand the probable action mechanism. The obtained results successfully confirmed the accuracy of employed methods to achieve high quality models for the toxin and its receptors within their lipid bilayers. Molecular dynamics analyses lead the structures to a more native like coordination. Moreover, the results of previous empirical studies were confirmed, while new insights for action mechanisms including the detailed roles of Hepatitis A virus cellular receptor 1 (HAVCR1) and Myelin and lymphocyte protein (MAL) proteins were achieved. In light of previous and our observations, we suggested novel models which elucidated the existing interplay between potential players of Epsilon toxin action mechanism with detailed structural evidences. These models would pave the way to have more robust understanding of the Epsilon toxin biology, more precise vaccine construction and more successful drug (inhibitor) design. (C) 2017 Elsevier Ltd. All rights reserved.

Item Type: Article
Keywords: Clostridium perfringens Epsilon toxin Structure modeling Molecular dynamics Protein docking raft-associated protein DNA vaccine dynamics pore toxicity mutant identification simulations expression solvation Pharmacology & Pharmacy Toxicology
Page Range: pp. 90-99
Journal or Publication Title: Toxicon
Journal Index: ISI
Volume: 127
Identification Number: https://doi.org/10.1016/j.toxicon.2017.01.010
ISSN: 0041-0101
Depositing User: مهندس مهدی شریفی
URI: http://eprints.dums.ac.ir/id/eprint/273

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