Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Wolters Kluwer full text link Wolters Kluwer Free PMC article
Full text links

Actions

Share

.2015 May-Jun;47(3):280-4.
doi: 10.4103/0253-7613.157123.

In silico analysis of potential inhibitors of Ca(2+) activated K(+) channel blocker, Charybdotoxin-C from Leiurus quinquestriatus hebraeus through molecular docking and dynamics studies

Affiliations

In silico analysis of potential inhibitors of Ca(2+) activated K(+) channel blocker, Charybdotoxin-C from Leiurus quinquestriatus hebraeus through molecular docking and dynamics studies

R Barani Kumar et al. Indian J Pharmacol.2015 May-Jun.

Abstract

Objective: Charybdotoxin-C (ChTx-C), from the scorpion Leiurus, quinquestriatus hebraeus blocks the calcium-activated potassium channels and causes hyper excitability of the nervous system. Detailed understanding the structure of ChTx-C, conformational stability, and intermolecular interactions are required to select the potential inhibitors of the toxin.

Materials and methods: The structure of ChTx-C was modeled using Modeller 9v7. The amino acid residues lining the binding site were predicted and used for toxin-ligand docking studies, further, selected toxin-inhibitor complexes were studied using molecular dynamics (MD) simulations.

Results: The predicted structure has 91.7% of amino acids in the core and allowed regions of Ramachandran plot. A total of 133 analog compounds of existing drugs for scorpion bites were used for docking. As a result of docking, a list of compounds was shown good inhibiting properties with target protein. By analyzing the interactions, Ser 15, Lys 32 had significant interactions with selected ligand molecules and Val5, which may have hydrophobic interaction with the cyclic group of the ligand. MD simulation studies revealed that the conformation and intermolecular interactions of all selected toxin-inhibitor complexes were stable.

Conclusion: The interactions of the ligand and active site amino acids were found out for the best-docked poses in turn helpful in designing potential antitoxins which may further be exploited in toxin based therapies.

Keywords: Antidote; homology modeling; inhibitors; ion channel blockers; neurotoxin.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: No.

Figures

Figure 1
Figure 1
Charybdotoxin-C modeling (a) Template-target alignment; (b) Predicted three-dimensional structure; (c) Ramachandran plot
Figure 2
Figure 2
(a) Potential energy profile; (b) root mean square deviation of modeled structure of Charybdotoxin-C over a period of 1 ns molecular dynamics simulation
Figure 3
Figure 3
The interactions of best inhibitors-Charybdotoxin-C docked complexes and the potential energy profile of (a) Mephenytoin; (b) Phensuximide; (c) Primidone; (d) Valproate; (e) Ethosuximide; (f) Fosphenytoin (g) Lamotringine; (h) Carbamazepine
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Karalliedde L. Animal toxins. Br J Anaesth. 1995;74:319–27. - PubMed
    1. Catterall WA, Cestèle S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T. Voltage-gated ion channels and gating modifier toxins. Toxicon. 2007;49:124–41. - PubMed
    1. Ledoux J, Werner ME, Brayden JE, Nelson MT. Calcium-activated potassium channels and the regulation of vascular tone. Physiology (Bethesda) 2006;21:69–78. - PubMed
    1. Vergara C, Latorre R, Marrion NV, Adelman JP. Calcium-activated potassium channels. Curr Opin Neurobiol. 1998;8:321–9. - PubMed
    1. Fuse N, Tsuchiya T, Nonomura Y, Menez A, Tamiya T. Structure of the snake short-chain neurotoxin, erabutoxin c, precursor gene. Eur J Biochem. 1990;193:629–33. - PubMed

MeSH terms

Substances

LinkOut - more resources

Full text links
Wolters Kluwer full text link Wolters Kluwer Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp