Interaction of polyethylene glycol with cytochrome c investigated via in vitro and in silico approaches

被引：0
作者：
Zahoor Ahmad Parray
Faizan Ahmad
Mohamed F. Alajmi
Afzal Hussain
Md. Imtaiyaz Hassan
Asimul Islam
机构：
[1] Centre for Interdisciplinary Research in Basic Sciences,Department of Pharmacognosy College of Pharmacy
[2] Jamia Millia Islamia,undefined
[3] King Saud University,undefined
来源：
Scientific Reports | / 11卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
One of the significant proteins that have attracted research groups due to virtue of being a potent selective anticancer drug target and property of triggering apoptosis upon release in cytoplasm is cytochrome c (cyt c). The mechanical transformations due to the macromolecular crowding in membrane in the mammalian cell are proposed to be useful inductors of changes in volume. It is very interesting to know that mitochondrial function were observed to be improved by polyethylene glycol (PEG) interaction, which in turn inhibits the cyt c (a pro-apoptotic cell death factor). In this work, the effect of polyethylene glycol of molecular weight 4 kilo Dalton (PEG 4 kDa) was investigated to highlight the structural transformations (tertiary and secondary structure) in cyt c using a choice of spectroscopic techniques (including UV–Vis absorption, near-UV, far-UV and Soret circular dichroism and fluorescence spectroscopy), which shows noteworthy shifts in the secondary and tertiary structures at higher concentrations of PEG 4 kDa with small changes in the heme-globular interactions. The size distribution changes of native protein treated with various concentrations of the crowder were observed and analyzed by dynamic light scattering (DLS). The interaction studies of the crowder with the protein was observed and analyzed by FTIR, isothermal titration calorimetry, time resolved fluorescence and molecular docking. The investigations suggested that the structural changes in the protein occurred due to soft interactions of PEG 4 kDa, which usually destabilizes proteins. The experimental evidence in this study proposed that crowding could be another approach to mechanical super-competition and free of certain markers that could aid in the identification and control of various diseases. This study suggests that crowders at specific concentrations, which softly interact with proteins, can be exploited as remedy for various diseases.
引用
收藏
相关论文
共 221 条
[11]  
Parray ZA(1990)On protein partitioning in two-phase aqueous polymer systems Bioseparation 1 191-1864
[12]  
Ahamad S(2007)Specific and non-specific interactions on non-porous carbon black surfaces Carbon 45 1854-165
[13]  
Ahmad F(2011)Effect of PEG chain length and hydrophilic weight fraction on polymersomes prepared from branched (PEG)(3)-PLA co-polymers Polym. Adv. Technol. 22 158-128
[14]  
Hassan MI(1991)Study of the molten globule intermediate state in protein folding by a hydrophobic fluorescent-probe Biopolymers 31 119-33
[15]  
Islam A(2003)Study of the serum albumin-polyethyleneglycol interaction to predict the protein partitioning in aqueous two-phase systems J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 798 25-72
[16]  
Parray ZA(2007)Effect of polyethylene glycols on the function and structure of thiol proteases J. Biochem. 142 65-389
[17]  
Shahid S(2013)PEG as a spacer arm markedly increases the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine J. Control. Release 172 382-69
[18]  
Ahmad F(1995)A branched monomethoxypoly(ethylene glycol) for protein modification Bioconjug. Chem. 6 62-642
[19]  
Hassan MI(2006)Effect of polyethylene glycol electrolyte balanced solution on patients with acute colonic pseudo obstruction after resolution of colonic dilation: a prospective, randomised, placebo controlled trial Gut 55 638-146
[20]  
Islam A(2001)Polyethylene glycol induces apoptosis in HT-29 cells: potential mechanism for chemoprevention of colon cancer FEBS Lett. 496 143-1136
12345678910