Issue 46, 2016

A comparative binding mechanism between human serum albumin and α-1-acid glycoprotein with corilagin: biophysical and computational approach

Abstract

The binding of corilagin with plasma serum proteins like human serum albumin (HSA) and α-1-acid glycoprotein (AGP) was investigated under physiological conditions. To understand the pharmacological importance of the corilagin molecule, anti-inflammatory activity on mouse macrophages (RAW 264.7) cell lines was studied. This study reveals that corilagin caused an increase in inhibition growth of inflamed macrophages in concentration-dependent manner with an IC50 value of 66 μM. Further, intrinsic fluorescence of HSA and AGP was quenched upon titration of corilagin, and the binding constants obtained from fluorescence emission was found to be Kcorilagin 4.2 ± 0.02 × 105 M−1 which corresponds to the free energy of −7.6 kcal M−1 at 25 °C for a HSA–corilagin complex. Interestingly, corilagin showed binding with AGP, an acute phase protein, and the binding constant was found to be Kcorilagin = 1.5 ± 0.01 × 104 M−1 and its free energy was −5.6 kcal M−1 at 25 °C. Further, the average binding distance, r, between the donor (HSA) and acceptor (corilagin) was calculated and found to be 1.32 nm according to Förster's theory of non-radiation energy transfer. Later, circular dichroism studies emphasized that there are marginal changes in secondary structural conformation of HSA in the presence of corilagin. Corilagin is specifically bound to site I of HSA which was proved by site specific marker, phenylbutazone. Furthermore, the binding details between corilagin and HSA revealed that corilagin was bound to subdomain IIA through multiple interactions like hydrogen bonding and hydrophobic effects. Molecular dynamic studies (MD) also suggest that binding is very precise to site I (IIA domain) on HSA. Also, MD studies showed that HSA–corilagin complex reaches equilibration state at around 4 ns, which proves that the HSA–corilagin complex is stable in nature, hence the experimental and computational results are in agreement. Thus, examining the interaction mechanism of corilagin with plasma proteins may play a critical role in developing corilagin inspired drugs.

Graphical abstract: A comparative binding mechanism between human serum albumin and α-1-acid glycoprotein with corilagin: biophysical and computational approach

Supplementary files

Article information

Article type
Paper
Submitted
15 mar 2016
Accepted
06 abr 2016
First published
07 abr 2016

RSC Adv., 2016,6, 40225-40237

A comparative binding mechanism between human serum albumin and α-1-acid glycoprotein with corilagin: biophysical and computational approach

D. P. Yeggoni, A. Rachamallu and R. Subramanyam, RSC Adv., 2016, 6, 40225 DOI: 10.1039/C6RA06837E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements