Skip to main content
SpringerLink
Log in

Molecular interaction of PCB180 to human serum albumin: insights from spectroscopic and molecular modelling studies

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

Polychlorinated biphenyls (PCBs) are potentially hazardous to the environment because of their chemical stability and biological toxicity. In this study, we identified the binding mode of a representative PCB180 to human serum albumin (HSA) using fluorescence and molecular dynamics (MD) simulation methods. PCB180 bound exactly at subdomain IIIA of HSA based on the fluorescence study along with site marker displacement experiments. PCB180 also induced conformational changes that were governed mainly by hydrophobic forces. MD studies and free energy calculations also made important contributions to the understanding of the effects of an HSA-PCB180 system on conformational changes. The simulations on binding behavior proved that PCB180 was located only in subdomain IIIA. Hydrophobic interactions dominated the mode of binding behavior. The results obtained using the two methods correlated well with each other. Our findings provide a framework for elucidating the mechanisms of PCB180-HSA binding, and may also help in further research on the transportation, distribution, and toxicity effects of PCBs when introduced into human blood serum.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2a–d
Fig. 3a–d
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Kavlock RJ, Daston GP, DeRosa C, Fenner-Crisp P, Gray LE, Kaattari S, Lucier G, Luster M, Mac MJ, Maczka C, Miller R, Moore J, Rolland R, Scott G, Sheehan DM, Sinks T, Tilson HA (1996) Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop. Environ Health Perspect 104:715–740

    Article  Google Scholar 

  2. Wehrmeier A, Lenoir D, Schramm LW, Zimmermann R, Hahn K, Henkelmann B, Kettup A (1998) Patterns of isomers of chlorinated dibenzo-p-dioxins as tool for elucidation of thermal formation mechanisms. Chemosphere 36:2775–2801

    Article  CAS  Google Scholar 

  3. Giesy JP, Kannan K (1998) Dioxin-like and Non-dioxin-like toxic effects of polychlorinated biphenyls (PCBs): implications for risk assessment. Crit Rev Toxicol 28:511–569

    Article  CAS  Google Scholar 

  4. Sanchez E, Fernandez SM, Lopez-Aparicio P, Recio MN, Perez-Albarsanz MA (2000) Selective fatty acid release from intracellular phospholipids caused by PCBs in rat renal tubular cell cultures. Chem Biol Interact 125:117–131

    Article  CAS  Google Scholar 

  5. Howard AS, Fitzpatrick R, Pessah I, Kostyniak P, Lein PJ (2003) Polychlorinated biphenyls induce caspase-dependent cell death in cultured embryonic rat hippocampal but not cortical neurons via activation of the ryanodine receptor. Toxicol Appl Pharmacol 190:72–86

    Article  CAS  Google Scholar 

  6. Kester MH, Bulduk S, Tibboel D, Meinl W, Glatt H, Falany CN, Coughtrie MW, Bergman A, Safe SH, Kuiper GG, Schuur AG, Brouwer A, Visser TJ (2000) Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs. Endocrinology 141:1897–1900

    Article  CAS  Google Scholar 

  7. Inglefield JR, Mundy WR, Meacham CA, Shafer TJ (2002) Identification of calcium-dependent and -independent signaling pathways involved in polychlorinated biphenyl-induced cyclic AMP-responsive element-binding protein phosphorylation in developing cortical neurons. Neuroscience 115:559–573

    Article  CAS  Google Scholar 

  8. Zolese G, Falcioni G, Bertoli E, Galeazzi R, Wozniak M, Wypych Z, Gratton E, Ambrosini A (2000) Steady-state and time resolved fluorescence of albumins interacting with N-oleylethanolamine, a component of the endogenous N-acylethanolamines. Proteins 40:39–48

    Article  CAS  Google Scholar 

  9. Petitpas I, Grnne T, Bhattacharya AA, Curry S (2001) Crystal structures of human serum albumin complexed with monounsaturated and polyunsaturated fatty acids. J Mol Biol 314:955–960

    Article  CAS  Google Scholar 

  10. Ghuman J, Zunszain PA, Petitpas I, Bhattacharya AA, Otagiri M, Curry S (2005) Structural basis of the drug-binding specificity of human serum albumin. J Mol Biol 353:38–52

    Article  CAS  Google Scholar 

  11. Curry S, Mandelkow H, Brick P, Franks N (1998) Crystal structure of human serum albumin complexed with monounsaturated and polyunsaturated fatty acid. Nat Struct Biol 5:827–835

    Article  CAS  Google Scholar 

  12. Fehske KJ, Mullar WE, Wollart U (1981) The location of drug binding sites in human serum albumin. Biochem Pharmacol 30:687–692

    Article  CAS  Google Scholar 

  13. Khan SN, Islam B, Yennamalli R, Sultan A, Subbarao N, Khan AU (2008) Interaction of mitoxantrone with human serum albumin: Spectroscopic and molecular modeling studies. Eur J Pharm Sci 35:371–382

    Article  CAS  Google Scholar 

  14. Deeb O, Rosales-Hernández MC, Gómez-Castro C, Garduño-Juárez R, Correa-Basurto J (2010) Exploration of human serum albumin binding sites by docking and molecular dynamics flexible ligand-protein interactions. Biopolymers 93:161–170

    Article  CAS  Google Scholar 

  15. Herve F, Urien S, Albengres E, Duche JC, Tillement JP (1994) Drug binding in plasma: a summary of recent trends in the study of drug and hormone binding. Clin Pharmacokinet 26:44–58

    Article  CAS  Google Scholar 

  16. Houde M, Martin JW, Letcher RJ, Solomon KR, Muir DCG (2006) Biological monitoring of polyfluoroalkyl compounds: a critical review. Environ Sci Technol 40:3463–3473

    Article  CAS  Google Scholar 

  17. Lejon S, Cramer JF, Nordberg PA (2008) Structural basis for the binding of naproxen to human serum albumin in the presence of fatty acids and the ga module. Acta Crystallogr F 64:64–69

    Article  CAS  Google Scholar 

  18. Patel S, Datta A (2007) Steady state and time-resolved fluorescence investigation of the specific binding of Two chlorin derivatives with human serum albumin. J Phys Chem B 111:10557–10562

    Article  CAS  Google Scholar 

  19. Purcell M, Neault JF, Malonga H, Arakawa H, Carpentier R, Tajmir-Riahi HA (2001) Interactions of atrazine and 2,4-D with human serum albumin studied by gel and capillary electrophoresis and FTIR spectroscopy. Biochim Biophys Acta 1548:129–138

    Article  CAS  Google Scholar 

  20. Saquib Q, Al-Khedhairy AA, Siddiqui MA, Roy AS, Dasgupta S, Musarrat J (2011) Preferential binding of insecticide phorate with sub-domain IIA of human serum albumin induces protein damage and its toxicological significance. Food Chem Toxicol 49:1787–1795

    Article  CAS  Google Scholar 

  21. Xie XY, Wang XR, Xu XM, Sun HJ, Chen XG (2010) Investigation of the interaction between endocrine disruptor bisphenol A and human serum albumin. Chemosphere 80:1075–1080

    Article  CAS  Google Scholar 

  22. Fujiwara S, Amisaki T (2008) Identification of high affinity fatty acid binding sites on human serum albumin by MM-PBSA method. Biophys J 94:95–103

    Article  CAS  Google Scholar 

  23. Quevedo MA, Ribone SR, Moroni GN, Brinon MC (2008) Binding to human serum albumin of zidovudine (AZT) and novel AZT derivatives. Bioorg Med Chem 16:2779–2790

    Article  CAS  Google Scholar 

  24. Sudhamalla B, Gokara M, Ahalawat N, Amooru DG, Subramanyam R (2010) Molecular dynamics simulation and binding studies of β-sitosterol with human serum albumin and its biological relevance. J Phys Chem B 114:9054–9062

    Article  CAS  Google Scholar 

  25. Safe SH (1994) Polychlorinated-biphenyls (PCBs)-environmental-impact, biochemical and toxic responses, and implications for risk assessment. Crit Rev Toxicol 24:87–149

    Article  CAS  Google Scholar 

  26. Rahman MH, Maruyama T, Okada T, Yamasaki K, Otagiri M (1993) Study of interaction of carprofen and its enantiomers with human serum albumin-I. Stereoselective site-to-site displacement of carprofen by ibuprofen. Biochem Pharmacol 46:1721–1731

    Article  CAS  Google Scholar 

  27. Petitpas I, Bhattacharya AA, Twine S, East M, Curry S (2001) Crystal structure analysis of warfarin binding to human serum albumin: anatomy of drug site I. J Biol Chem 276:22804–22809

    Article  CAS  Google Scholar 

  28. Anderson AC, O’Neil RH, Surti TS, Stroud RM (2001) Approaches to solving the rigid receptor problem by identifying a minimal set of flexible residues during ligand docking. Chem Biol 8:445–457

    Article  CAS  Google Scholar 

  29. Sherman W, Day T, Jacobson MP, Friesner RA, Farid R (2006) Novel procedure for modeling ligand/receptor induced fit effects. J Med Chem 49:534–553

    Article  CAS  Google Scholar 

  30. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19:1639–1662

    Article  CAS  Google Scholar 

  31. Case DA, Darden TA, Cheatham TE, III Simmerling CL, Wang J, Duke RE, Luo R, Walker RC, Zhang W, Merz KM, Roberts B, Wang B, Hayik S, Roitberg A, Seabra G, Kolossvai I, Wong KF, Paesani F, Vanicek J, Liu J, Wu X, Brozell SR, Steinbrecher T, Gohlke H, Cai Q, Ye X, Wang J, Hsieh MJ, Cui G, Roe DR, Mathews DH, Seetin MG, Sagui C, Babin V, Luchko T, Gusarov S, Kovalenko A, Kollman PA (2010) AMBER 11. http://ambermd.org/

  32. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general AMBER force field. J Comput Chem 25:1157–1174

    Article  CAS  Google Scholar 

  33. Kollman PA, Massova I, Reyes C, Kuhn B, Huo SH, Chong L, Lee M, Lee T, Duan Y, Wang W, Donini O, Cieplak P, Srinivasan J, Case DA, Cheatham TE (2000) Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res 33:889–897

    Article  CAS  Google Scholar 

  34. Ross PD, Subramanian S (1981) Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 20:3096–3102

    Article  CAS  Google Scholar 

  35. Gao H, Lei L, Liu J, Qin K, Chen X, Hu Z (2004) The study on the interaction between human serum albumin and a new reagent with antitumour activity by spectrophotometric methods. J Photochem Photobiol A 167:213–221

    Article  CAS  Google Scholar 

  36. Pandey RK, Constantine S, Tsuchida T, Zheng G, Medforth CJ, Aoudia M, Kozyrev AN, Rodgers MAJ, Kato H, Smith KM, Dougherty TJ (1997) Synthesis photophysical properties in vivo photosensitizing efficacy and human serum albumin binding properties of some novel bacteriochlorins. J Med Chem 40:2770–2779

    Article  CAS  Google Scholar 

  37. Consuelo Jiménez M, Miranda MA, Vayá I (2005) Triplet excited states as chiral reporters for the binding of drugs to transport proteins. J Am Chem Soc 127:10134–10135

    Article  CAS  Google Scholar 

  38. Sułkowska A, Maciążek-Jurczyk M, Bojko B, Równicka J, Zubik-Skupień I, Temba E, Pentak D, Sułkowski WW (2008) Competitive binding of phenylbutazone and colchicines to serum albumin in multidrug therapy: a spectroscopic study. J Mol Struct 881:97–106

    Article  CAS  Google Scholar 

  39. Eliard PH, Rousseau GG (1984) Biochem J 18:395

    Google Scholar 

Download references

Acknowledgments

This work was supported financially by National Natural Science Foundation of China (NO. 31000017) (NO. 21207056), the Natural Foundation of Gansu Province (1104WCGA187) and Key Laboratory of Chemistry and Quality for Traditional Chinese Medicines of the College of Gansu Province, Gansu College of Traditional Chinese Medicine (Zzy-2011-03).

Author information

Authors and Affiliations

  1. School of Pharmacy, LanzhouUniversity, Lanzhou, 730000, China

    Senbiao Fang, Huanhuan Li, Tao Liu, Hongxia Xuan & Chunyan Zhao

  2. College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, 471003, China

    Xin Li

Authors
  1. Senbiao Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huanhuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hongxia Xuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chunyan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chunyan Zhao.

Additional information

Senbiao Fang and Huanhuan Li contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig. S1

(DOC 30 kb)

Fig. S2

(DOC 35 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fang, S., Li, H., Liu, T. et al. Molecular interaction of PCB180 to human serum albumin: insights from spectroscopic and molecular modelling studies. J Mol Model 20, 2098 (2014). https://doi.org/10.1007/s00894-014-2098-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00894-014-2098-7

Keywords

Search

Navigation