Skip to main content
SpringerLink
Log in

Revealing the structural dynamics of feline serum albumin

  • Original Research
  • Published:
Structural Chemistry Aims and scope Submit manuscript

Abstract

Serum albumin (SA) is a prevalent carrier protein in blood. SA carries a diverse range of nutrients, drugs, and metal ions. It has wide clinical and biochemical applications. In veterinary use, human serum albumin (HSA) was administered to increase albumin level and osmotic pressure in critically ill dogs and cats, but this therapy is very expensive and under debate. Using other albumins is one of the alternatives for a cross-species usage. Thus, understanding structural dynamics of albumins from other animals becomes essential. In this work, feline serum albumin (FSA) is computationally studied in comparison with bovine (BSA), canine (CSA), and human (HSA) serum albumins from a previous work for the first time. FSA shares high sequence identity to CSA, but its dynamics resembles HSA and BSA. Like other albumins, the different movement of domains I and III is a signature of each albumin. FSA shows similar size of Sudlow site I to BSA and HSA, whereas its Sudlow site II is smaller. This permits the different drug-binding affinity of FSA at Sudlow site II. Furthermore, C34 in FSA is more flexible than HSA due to no interaction with Y84 that anchors C34 on a protein surface. An increased flexibility of C34 thiol group can easily trigger undesired thiolation or dimerization. Although FSA shares similar dynamics to HSA, its different ligand-binding affinity can be a key weakness to serve as a HSA substitute in cross-species animals.

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. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

FSA:

Feline serum albumin

BSA:

Bovine serum albumin

CSA:

Canine serum albumin

HSA:

Human serum albumin

MD:

Molecular dynamics

References

  1. Teng Y, Liu R, Li C, Xia Q, Zhang P (2011) The interaction between 4-aminoantipyrine and bovine serum albumin: multiple spectroscopic and molecular docking investigations. J Hazard Mater 190(1–3):574–581. https://doi.org/10.1016/j.jhazmat.2011.03.084

    Article  CAS  PubMed  Google Scholar 

  2. Sleep D (2015) Albumin and its application in drug delivery. Expert Opin Drug Deliv 12(5):793–812. https://doi.org/10.1517/17425247.2015.993313

    Article  CAS  PubMed  Google Scholar 

  3. Qi J, Zhang Y, Gou Y, Lee P, Wang J, Chen S, Zhou Z, Wu X, Yang F, Liang H (2016) Multidrug delivery systems based on human serum albumin for combination therapy with three anticancer agents. Mol Pharm 13(9):3098–3105. https://doi.org/10.1021/acs.molpharmaceut.6b00277

    Article  CAS  PubMed  Google Scholar 

  4. Apiwat C, Luksirikul P, Kankla P, Pongprayoon P, Treerattrakoon K, Paiboonsukwong K, Fucharoen S, Dharakul T, Japrung D (2016) Graphene based aptasensor for glycated albumin in diabetes mellitus diagnosis and monitoring. Biosens Bioelectron 82:140–145. https://doi.org/10.1016/j.bios.2016.04.015

    Article  CAS  PubMed  Google Scholar 

  5. Chien SC, Chen CY, Lin CF, Yeh HI (2017) Critical appraisal of the role of serum albumin in cardiovascular disease. Biomark Res 5:31. https://doi.org/10.1186/s40364-017-0111-x

    Article  PubMed  PubMed Central  Google Scholar 

  6. Naldi M, Baldassarre M, Nati M, Laggetta M, Giannone FA, Domenicali M, Bernardi M, Caraceni P, Bertucci C (2015) Mass spectrometric characterization of human serum albumin dimer: a new potential biomarker in chronic liver diseases. J Pharm Biomed 112:169–175. https://doi.org/10.1016/j.jpba.2014.12.001

    Article  CAS  Google Scholar 

  7. Bujacz A (2012) Structures of bovine, equine and leporine serum albumin. Acta Crystallogr D Biol Crystallogr 68(Pt 10):1278–1289. https://doi.org/10.1107/S0907444912027047

    Article  CAS  PubMed  Google Scholar 

  8. Mathews KA (2008) The therapeutic use of 25% human serum albumin in critically ill dogs and cats. Vet Clin North Am Small Anim Pract 38(3):595–605, xi-xii. https://doi.org/10.1016/j.cvsm.2008.02.004

    Article  PubMed  Google Scholar 

  9. Horowitz FB, Read RL, Powell LL (2015) A retrospective analysis of 25% human serum albumin supplementation in hypoalbuminemic dogs with septic peritonitis. Can Vet J 56(6):591–597

    PubMed  PubMed Central  Google Scholar 

  10. Vigano F, Perissinotto L, Bosco VR (2010) Administration of 5% human serum albumin in critically ill small animal patients with hypoalbuminemia: 418 dogs and 170 cats (1994-2008). J Vet Emerg Crit Care (San Antonio) 20(2):237–243. https://doi.org/10.1111/j.1476-4431.2010.00526.x

    Article  Google Scholar 

  11. Zsila F (2013) Subdomain IB is the third major drug binding region of human serum albumin: toward the three-sites model. Mol Pharm 10(5):1668–1682. https://doi.org/10.1021/mp400027q

    Article  CAS  PubMed  Google Scholar 

  12. Nakashima F, Shibata T, Kamiya K, Yoshitake J, Kikuchi R, Matsushita T, Ishii I, Gimenez-Bastida JA, Schneider C, Uchida K (2018) Structural and functional insights into S-thiolation of human serum albumins. Sci Rep 8(1):932. https://doi.org/10.1038/s41598-018-19610-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Narazaki R, Maruyama T, Otagiri M (1997) Probing the cysteine 34 residue in human serum albumin using fluorescence techniques. Biochim Biophys Acta 1338(2):275–281. https://doi.org/10.1016/s0167-4838(96)00221-x

    Article  CAS  PubMed  Google Scholar 

  14. Bertucci C, Domenici E (2002) Reversible and covalent binding of drugs to human serum albumin: methodological approaches and physiological relevance. Curr Med Chem 9(15):1463–1481. https://doi.org/10.2174/0929867023369673

    Article  CAS  PubMed  Google Scholar 

  15. Kratz F (2008) Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Release 132(3):171–183. https://doi.org/10.1016/j.jconrel.2008.05.010

    Article  CAS  PubMed  Google Scholar 

  16. Williams AM, Dickinson RG (1994) Studies on the reactivity of acyl glucuronides--VI. Modulation of reversible and covalent interaction of diflunisal acyl glucuronide and its isomers with human plasma protein in vitro. Biochem Pharmacol 47(3):457–467. https://doi.org/10.1016/0006-2952(94)90176-7

    Article  CAS  PubMed  Google Scholar 

  17. Ketrat S, Japrung D, Pongprayoon P (2020) Exploring how structural and dynamic properties of bovine and canine serum albumins differ from human serum albumin. J Mol Graph Model 98:107601. https://doi.org/10.1016/j.jmgm.2020.107601

    Article  CAS  PubMed  Google Scholar 

  18. Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ (2009) Jalview version 2--a multiple sequence alignment editor and analysis workbench. Bioinformatics 25(9):1189–1191. https://doi.org/10.1093/bioinformatics/btp033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yokomaku K, Akiyama M, Morita Y, Kihira K, Komatsu T (2018) Core-shell protein clusters comprising haemoglobin and recombinant feline serum albumin as an artificial O2 carrier for cats. J Mater Chem B 6(16):2417–2425. https://doi.org/10.1039/c8tb00211h

    Article  CAS  PubMed  Google Scholar 

  20. Yamada K, Yokomaku K, Kureishi M, Akiyama M, Kihira K, Komatsu T (2016) Artificial blood for dogs. Sci Rep 6:36782. https://doi.org/10.1038/srep36782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Awang T, Wiriyatanakorn N, Saparpakorn P, Japrung D, Pongprayoon P (2016) Understanding the effects of two bound glucose in Sudlow site I on structure and function of human serum albumin: theoretical studies. J Biomol Struct Dyn:1–23. https://doi.org/10.1080/07391102.2016.1160841

  22. Panman W, Japrung D, Pongprayoon P (2016) Exploring the interactions of a DNA aptamer with human serum albumins: simulation studies. J Biomol Struct Dyn:1–9. https://doi.org/10.1080/07391102.2016.1224733

  23. Pongprayoon P, Gleeson MP (2014) Probing the binding site characteristics of HSA: a combined molecular dynamics and cheminformatics investigation. J Mol Graph Model 54:164–173. https://doi.org/10.1016/j.jmgm.2014.10.007

    Article  CAS  PubMed  Google Scholar 

  24. Webb B, Sali A (2016) Comparative protein structure modeling using MODELLER. Curr Protoc Bioinformatics 54:5 6 1–5 6 37. https://doi.org/10.1002/cpbi.3

    Article  Google Scholar 

  25. Niramitranon J, Sansom MS, Pongprayoon P (2016) Why do the outer membrane proteins OmpF from E. coli and OprP from P. aeruginosa prefer trimer? Simulation studies. J Mol Graph Model 65:1–7. https://doi.org/10.1016/j.jmgm.2016.02.002

    Article  CAS  PubMed  Google Scholar 

  26. Lindahl E, Hess B, van der Spoel D (2001) GROMACS 3.0: a package for molecular simulation and trajectory analysis. J Mol Model 7:306–317

    Article  CAS  Google Scholar 

  27. Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an N·log(N) method for Ewald sums in large systems. J Chem Phys 98(12):10089–10092

    Article  CAS  Google Scholar 

  28. Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81(8):3684–3690

    Article  CAS  Google Scholar 

  29. Humphrey W, Dalke A, Schulten K (1996) VMD - visual molecular dynamics. J Mol Graph 14:33–38

    Article  CAS  PubMed  Google Scholar 

  30. Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S (2003) Crystal structural analysis of human serum albumin complexed with hemin and fatty acid. BMC Struct Biol 3:6. https://doi.org/10.1186/1472-6807-3-6

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ryan AJ, Chung CW, Curry S (2011) Crystallographic analysis reveals the structural basis of the high-affinity binding of iophenoxic acid to human serum albumin. BMC Struct Biol 11:18. https://doi.org/10.1186/1472-6807-11-18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zunszain PA, Ghuman J, McDonagh AF, Curry S (2008) Crystallographic analysis of human serum albumin complexed with 4Z,15E-bilirubin-IXalpha. J Mol Biol 381(2):394–406. https://doi.org/10.1016/j.jmb.2008.06.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhu L, Yang F, Chen L, Meehan EJ, Huang M (2008) A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography. J Struct Biol 162(1):40–49. https://doi.org/10.1016/j.jsb.2007.12.004

    Article  CAS  PubMed  Google Scholar 

  34. Curry S, Mandelkow H, Brick P, Franks N (1998) Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites. Nat Struct Biol 5(9):827–835. https://doi.org/10.1038/1869

    Article  CAS  PubMed  Google Scholar 

  35. Yang F, Bian C, Zhu L, Zhao G, Huang Z, Huang M (2007) Effect of human serum albumin on drug metabolism: structural evidence of esterase activity of human serum albumin. J Struct Biol 157(2):348–355. https://doi.org/10.1016/j.jsb.2006.08.015

    Article  CAS  PubMed  Google Scholar 

  36. 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(1):38–52. https://doi.org/10.1016/j.jmb.2005.07.075

    Article  CAS  PubMed  Google Scholar 

  37. Ryan AJ, Ghuman J, Zunszain PA, Chung CW, Curry S (2011) Structural basis of binding of fluorescent, site-specific dansylated amino acids to human serum albumin. J Struct Biol 174(1):84–91. https://doi.org/10.1016/j.jsb.2010.10.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Majorek KA, Porebski PJ, Dayal A, Zimmerman MD, Jablonska K, Stewart AJ, Chruszcz M, Minor W (2012) Structural and immunologic characterization of bovine, horse, and rabbit serum albumins. Mol Immunol 52(3–4):174–182. https://doi.org/10.1016/j.molimm.2012.05.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Chruszcz M, Mikolajczak K, Mank N, Majorek KA, Porebski PJ, Minor W (2013) Serum albumins-unusual allergens. Biochim Biophys Acta 1830(12):5375–5381. https://doi.org/10.1016/j.bbagen.2013.06.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tanabe S, Kobayashi Y, Takahata Y, Morimatsu F, Shibata R, Nishimura T (2002) Some human B and T cell epitopes of bovine serum albumin, the major beef allergen. Biochem Biophys Res Commun 293(5):1348–1353. https://doi.org/10.1016/S0006-291X(02)00381-9

    Article  CAS  PubMed  Google Scholar 

  41. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23(21):2947–2948. https://doi.org/10.1093/bioinformatics/btm404

    Article  CAS  PubMed  Google Scholar 

  42. Unni S, Huang Y, Hanson RM, Tobias M, Krishnan S, Li WW, Nielsen JE, Baker NA (2011) Web servers and services for electrostatics calculations with APBS and PDB2PQR. J Comput Chem 32(7):1488–1491. https://doi.org/10.1002/jcc.21720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kuhlmann M, Hamming JBR, Voldum A, Tsakiridou G, Larsen MT, Schmokel JS, Sohn E, Bienk K, Schaffert D, Sorensen ES, Wengel J, Dupont DM, Howard KA (2017) An albumin-oligonucleotide assembly for potential combinatorial drug delivery and half-life extension applications. Mol Ther Nucleic acids 9:284–293. https://doi.org/10.1016/j.omtn.2017.10.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Schmokel J, Voldum A, Tsakiridou G, Kuhlmann M, Cameron J, Sorensen ES, Wengel J, Howard KA (2017) Site-selective conjugation of an anticoagulant aptamer to recombinant albumins and maintenance of neonatal Fc receptor binding. Nanotechnology 28(20):204004. https://doi.org/10.1088/1361-6528/aa6a9b

    Article  CAS  PubMed  Google Scholar 

  45. Levi V, Gonzalez Flecha FL (2002) Reversible fast-dimerization of bovine serum albumin detected by fluorescence resonance energy transfer. Biochim Biophys Acta 1599(1–2):141–148. https://doi.org/10.1016/s1570-9639(02)00414-4

    Article  CAS  PubMed  Google Scholar 

  46. Spiga O, Summa D, Cirri S, Bernini A, Venditti V, De Chiara M, Priora R, Frosali S, Margaritis A, Di Giuseppe D, Di Simplicio P, Niccolai N (2011) A structurally driven analysis of thiol reactivity in mammalian albumins. Biopolymers 95(4):278–285. https://doi.org/10.1002/bip.21577

    Article  CAS  PubMed  Google Scholar 

  47. Stewart AJ, Blindauer CA, Berezenko S, Sleep D, Tooth D, Sadler PJ (2005) Role of Tyr84 in controlling the reactivity of Cys34 of human albumin. FEBS J 272(2):353–362. https://doi.org/10.1111/j.1742-4658.2004.04474.x

    Article  CAS  PubMed  Google Scholar 

  48. Bonanata J, Turell L, Antmann L, Ferrer-Sueta G, Botasini S, Mendez E, Alvarez B, Coitino EL (2017) The thiol of human serum albumin: acidity, microenvironment and mechanistic insights on its oxidation to sulfenic acid. Free Radic Biol Med 108:952–962. https://doi.org/10.1016/j.freeradbiomed.2017.04.021

    Article  CAS  PubMed  Google Scholar 

  49. Wang X, Guo L, Ma H (2009) Analysis of local polarity change around Cys34 in bovine serum albumin during N-->B transition by a polarity-sensitive fluorescence probe. Spectrochim Acta A Mol Biomol Spectrosc 73(5):875–878. https://doi.org/10.1016/j.saa.2009.04.008

    Article  CAS  PubMed  Google Scholar 

  50. Kosa T, Maruyama T, Otagiri M (1997) Species differences of serum albumins: I. drug binding sites. Pharm Res 14(11):1607–1612. https://doi.org/10.1023/a:1012138604016

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

We would like to thank Kasetsart University Research and Development Institute (KURDI) and National Nanotechnology Center (NANOTEC, Grant no. P1751330) for financial support.

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand

    Prapasiri Pongprayoon

  2. Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, KU Institute for Advanced Studies, Kasetsart University, Bangkok, 10900, Thailand

    Prapasiri Pongprayoon

  3. National Nanotechnology Center, National Science and Technology Development Agency, Thailand Science Park, Pathumthani, 12120, Thailand

    Deanpen Japrung

Authors
  1. Prapasiri Pongprayoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deanpen Japrung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Prapasiri Pongprayoon or Deanpen Japrung.

Ethics declarations

Conflict of interest

The authors declare that they do not have any conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 614 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pongprayoon, P., Japrung, D. Revealing the structural dynamics of feline serum albumin. Struct Chem 32, 69–77 (2021). https://doi.org/10.1007/s11224-020-01619-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11224-020-01619-4

Keywords

Search

Navigation