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Protein stability, conformational change and binding mechanism of human serum albumin upon binding of embelin and its role in disease control

Paper ID Volume ID Publish Year Pages File Format Full-Text
29587 44422 2016 12 PDF Available
Title
Protein stability, conformational change and binding mechanism of human serum albumin upon binding of embelin and its role in disease control
Abstract

•Embelin exhibits anticancer activity against HeLa cell lines.•A strong HSA–embelin complex has been formed due to microenvironment change.•Embelin–HSA binds to subdomain IB through H-bonding and hydrophobic interaction.•The interaction between embelin and HSA was 1:1.•Molecular dynamics simulation shows that HSA–embelin complex was stable.

Here, we present the inclusive binding mode of phytochemical embelin, an anticancer drug with human serum albumin (HSA) established under physiological condition. Also, to understand the pharmacological role of embelin molecule, here, we have studied the anti-cancer activity of embelin on human cervical cancer cell line (HeLa cell line), which revealed that embelin showed dose dependent inhibition in the growth of cancer cells and also induces 26.3% of apoptosis at an IC50 value of 29 μM. Further, embelin was titrated with HSA and the fluorescence emission quenching of HSA due to the formation of the HSA–embelin complex was observed. The binding constant of this complex is 5.9 ± .01 × 104 M− 1 and the number of bound embelin molecules is approximately 1.0. Consequently, molecular displacement and computational docking experiments show that the embelin is binding to subdomain IB to HSA. Further evidence from microTOF-Q mass spectrometry showed an increase in mass from 66,563 Da to 66,857 Da observed for free HSA and HSA + embelin complex, signifying that there is robust binding of embelin with HSA. In addition, the variations of HSA secondary structural elements in presence of embelin were confirmed by circular dichroism which indicates partial unfolding of protein. Furthermore, the transmission electron micrographs established that complex formation leads to aggregation of HSA plus embelin. Molecular dynamics simulations revealed that the stability of the HSA–embelin complexes and results suggests that at around 3500 ps the complex reaches equilibration state which clearly contributes to the understanding of the stability of the HSA–embelin complexes.

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Keywords
Free energy; MicroTOF-Q; Protein–ligand interaction; Protein conformation; Molecular docking; Molecular dynamics simulations
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Protein stability, conformational change and binding mechanism of human serum albumin upon binding of embelin and its role in disease control
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 160, July 2016, Pages 248–259
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us