Analyze Diet
Proteins2014; 82(9); 2199-2208; doi: 10.1002/prot.24583

Structural studies of bovine, equine, and leporine serum albumin complexes with naproxen.

Abstract: Serum albumin, a protein naturally abundant in blood plasma, shows remarkable ligand binding properties of numerous endogenous and exogenous compounds. Most of serum albumin binding sites are able to interact with more than one class of ligands. Determining the protein-ligand interactions among mammalian serum albumins is essential for understanding the complexity of this transporter. We present three crystal structures of serum albumins in complexes with naproxen (NPS): bovine (BSA-NPS), equine (ESA-NPS), and leporine (LSA-NPS) determined to 2.58 Å (C2), 2.42 Å (P61), and 2.73 Å (P2₁2₁2₁) resolutions, respectively. A comparison of the structurally investigated complexes with the analogous complex of human serum albumin (HSA-NPS) revealed surprising differences in the number and distribution of naproxen binding sites. Bovine and leporine serum albumins possess three NPS binding sites, but ESA has only two. All three complexes of albumins studied here have two common naproxen locations, but BSA and LSA differ in the third NPS binding site. None of these binding sites coincides with the naproxen location in the HSA-NPS complex, which was obtained in the presence of other ligands besides naproxen. Even small differences in sequences of serum albumins from various species, especially in the area of the binding pockets, influence the affinity and the binding mode of naproxen to this transport protein.
Publication Date: 2014-04-29 PubMed ID: 24753230DOI: 10.1002/prot.24583Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The researchers analyzed the three-dimensional structure of complexes of serum albumins–proteins that carry substances in our blood–from cows, horses, and rabbits with the drug naproxen. They found that there are differences in the number and locations where naproxen attaches to these proteins between the different species and with humans.

Understanding Serum Albumin and Naproxen Complexes

  • Serum albumin is a protein that is naturally abundant in our blood and helps transport a wide range of substances.
  • Naproxen is a commonly used pain reliever that binds to serum albumin.
  • The researchers present crystal structures of serum albumins from bovines (cows), equines (horses), and leporines (rabbits) in combination with naproxen.

Differences in Binding Sites

  • The researchers found surprising differences in the number of binding sites where naproxen attaches to serum albumins from different species.
  • Cow and rabbit serum albumins have three naproxen binding sites, but horse serum albumin only has two.
  • All of the albumins studied have two common naproxen locations, but cow and rabbit albumins have a different location for the third binding site.

Comparison with Human Serum Albumin

  • The researchers also compared the animal serum albumins with human serum albumin (HSA).
  • Interestingly, none of the binding sites for naproxen on the animal albumins coincided with the binding site on HSA.
  • This observation was made even when HSA was examined in the presence of other substances that also bind to it.

Significance of the Findings

  • This study demonstrates that even small differences in the sequences of albumins between different species can impact how a drug like naproxen interacts with these proteins.
  • Understanding these variations could be important in determining how the drug is transported in the body and contributes to its efficacy and potential side effects.

Cite This Article

APA
Bujacz A, Zielinski K, Sekula B. (2014). Structural studies of bovine, equine, and leporine serum albumin complexes with naproxen. Proteins, 82(9), 2199-2208. https://doi.org/10.1002/prot.24583

Publication

ISSN: 1097-0134
NlmUniqueID: 8700181
Country: United States
Language: English
Volume: 82
Issue: 9
Pages: 2199-2208

Researcher Affiliations

Bujacz, Anna
  • Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 4/10, 90-924, Lodz, Poland.
Zielinski, Kamil
    Sekula, Bartosz

      MeSH Terms

      • Animals
      • Anti-Inflammatory Agents, Non-Steroidal / chemistry
      • Binding Sites
      • Cattle
      • Crystallography, X-Ray
      • Horses
      • Humans
      • Models, Molecular
      • Multiprotein Complexes / chemistry
      • Multiprotein Complexes / ultrastructure
      • Naproxen / chemistry
      • Protein Binding
      • Protein Conformation
      • Rabbits
      • Serum Albumin / chemistry
      • Serum Albumin / ultrastructure

      Citations

      This article has been cited 40 times.
      1. Göktürk T, Sakallı Çetin E, Hökelek T, Pekel H, Şensoy Ö, Aksu EN, Güp R. Synthesis, Structural Investigations, DNA/BSA Interactions, Molecular Docking Studies, and Anticancer Activity of a New 1,4-Disubstituted 1,2,3-Triazole Derivative. ACS Omega 2023 Sep 5;8(35):31839-31856.
        doi: 10.1021/acsomega.3c03355pubmed: 37692230google scholar: lookup
      2. Petrova V, Yonkova P, Simeonova G, Vachkova E. Horse serum potentiates cellular viability and improves indomethacin-induced adipogenesis in equine subcutaneous adipose-derived stem cells (ASCs). Int J Vet Sci Med 2023;11(1):94-105.
        doi: 10.1080/23144599.2023.2248805pubmed: 37655053google scholar: lookup
      3. Kim SB, Kamiya G, Furuta T, Kitada N, Maki SA. Coelenterazine Indicators for the Specific Imaging of Human and Bovine Serum Albumins. Sensors (Basel) 2023 Jun 29;23(13).
        doi: 10.3390/s23136020pubmed: 37447868google scholar: lookup
      4. Meng R, Zhu H, Deng P, Li M, Ji Q, He H, Jin L, Wang B. Research progress on albumin-based hydrogels: Properties, preparation methods, types and its application for antitumor-drug delivery and tissue engineering. Front Bioeng Biotechnol 2023;11:1137145.
        doi: 10.3389/fbioe.2023.1137145pubmed: 37113668google scholar: lookup
      5. Eichhorn T, Kolbe F, Mišić S, Dimić D, Morgan I, Saoud M, Milenković D, Marković Z, Rüffer T, Dimitrić Marković J, Kaluđerović GN. Synthesis, Crystallographic Structure, Theoretical Analysis, Molecular Docking Studies, and Biological Activity Evaluation of Binuclear Ru(II)-1-Naphthylhydrazine Complex. Int J Mol Sci 2022 Dec 30;24(1).
        doi: 10.3390/ijms24010689pubmed: 36614131google scholar: lookup
      6. Czub MP, Stewart AJ, Shabalin IG, Minor W. Organism-specific differences in the binding of ketoprofen to serum albumin. IUCrJ 2022 Sep 1;9(Pt 5):551-561.
        doi: 10.1107/S2052252522006820pubmed: 36071810google scholar: lookup
      7. Monaco S, Ramírez-Cárdenas J, Carmona AT, Robina I, Angulo J. Inter-Ligand STD NMR: An Efficient 1D NMR Approach to Probe Relative Orientation of Ligands in a Multi-Subsite Protein Binding Pocket. Pharmaceuticals (Basel) 2022 Aug 21;15(8).
        doi: 10.3390/ph15081030pubmed: 36015178google scholar: lookup
      8. Zhuo W, Peng X, Lin X. Insights into the interaction mechanism between tiagabine hydrochloride and two serum albumins. RSC Adv 2018 Jul 9;8(44):24953-24960.
        doi: 10.1039/c8ra04153apubmed: 35542170google scholar: lookup
      9. Zdovc B, Jaklin M, Hribar-Lee B, Lukšič M. Influence of Low Molecular Weight Salts on the Viscosity of Aqueous-Buffer Bovine Serum Albumin Solutions. Molecules 2022 Feb 1;27(3).
        doi: 10.3390/molecules27030999pubmed: 35164264google scholar: lookup
      10. Zhang L, Yu H, Bai Y, Mishra B, Yang X, Wang J, Yu EB, Li R, Chen X. A Neoglycoprotein-Immobilized Fluorescent Magnetic Bead Suspension Multiplex Array for Galectin-Binding Studies. Molecules 2021 Oct 14;26(20).
        doi: 10.3390/molecules26206194pubmed: 34684775google scholar: lookup
      11. Al-Raqa SY, Khezami K, Kaya EN, Kocak A, Durmuş M. Experimental and theoretical investigation of water-soluble silicon(IV) phthalocyanine and its interaction with bovine serum albumin. J Biol Inorg Chem 2021 May;26(2-3):235-247.
        doi: 10.1007/s00775-021-01848-wpubmed: 33558997google scholar: lookup
      12. Vita GM, De Simone G, Leboffe L, Montagnani F, Mariotti D, Di Bella S, Luzzati R, Gori A, Ascenzi P, di Masi A. Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects. Front Immunol 2020;11:507092.
        doi: 10.3389/fimmu.2020.507092pubmed: 33363530google scholar: lookup
      13. Perontsis S, Geromichalou E, Perdih F, Hatzidimitriou AG, Geromichalos GD, Turel I, Psomas G. Synthesis, structural determination, in vitro and in silico biological evaluation of divalent or trivalent cobalt complexes with indomethacin. J Inorg Biochem 2020 Nov;212:111213.
      14. Czub MP, Handing KB, Venkataramany BS, Cooper DR, Shabalin IG, Minor W. Albumin-Based Transport of Nonsteroidal Anti-Inflammatory Drugs in Mammalian Blood Plasma. J Med Chem 2020 Jul 9;63(13):6847-6862.
        doi: 10.1021/acs.jmedchem.0c00225pubmed: 32469516google scholar: lookup
      15. Jiao Q, Zhang W, Jiang Y, Jiang L, Chen X, Liu B. Study on the Interactions Between Caffeoylquinic Acids With Bovine Serum Albumin: Spectroscopy, Antioxidant Activity, LC-MS(n), and Molecular Docking Approach. Front Chem 2019;7:840.
        doi: 10.3389/fchem.2019.00840pubmed: 31867307google scholar: lookup
      16. Castagna R, Donini S, Colnago P, Serafini A, Parisini E, Bertarelli C. Biohybrid Electrospun Membrane for the Filtration of Ketoprofen Drug from Water. ACS Omega 2019 Aug 20;4(8):13270-13278.
        doi: 10.1021/acsomega.9b01442pubmed: 31460455google scholar: lookup
      17. Czub MP, Venkataramany BS, Majorek KA, Handing KB, Porebski PJ, Beeram SR, Suh K, Woolfork AG, Hage DS, Shabalin IG, Minor W. Testosterone meets albumin - the molecular mechanism of sex hormone transport by serum albumins. Chem Sci 2019 Feb 14;10(6):1607-1618.
        doi: 10.1039/c8sc04397cpubmed: 30842823google scholar: lookup
      18. Szekeres GP, Kneipp J. SERS Probing of Proteins in Gold Nanoparticle Agglomerates. Front Chem 2019;7:30.
        doi: 10.3389/fchem.2019.00030pubmed: 30766868google scholar: lookup
      19. Zhang DD, Liu JL, Jiang TM, Li L, Fang GZ, Liu YP, Chen LJ. Influence of Kluyveromyces marxianus on proteins, peptides, and amino acids in Lactobacillus-fermented milk. Food Sci Biotechnol 2017;26(3):739-748.
        doi: 10.1007/s10068-017-0094-2pubmed: 30263599google scholar: lookup
      20. Bujacz A, Talaj JA, Zielinski K, Pietrzyk-Brzezinska AJ, Neumann P. Crystal structures of serum albumins from domesticated ruminants and their complexes with 3,5-diiodosalicylic acid. Acta Crystallogr D Struct Biol 2017 Nov 1;73(Pt 11):896-909.
        doi: 10.1107/S205979831701470Xpubmed: 29095162google scholar: lookup
      21. Hauser M, Qian C, King ST, Kauffman S, Naider F, Hettich RL, Becker JM. Identification of peptide-binding sites within BSA using rapid, laser-induced covalent cross-linking combined with high-performance mass spectrometry. J Mol Recognit 2018 Feb;31(2).
        doi: 10.1002/jmr.2680pubmed: 28994207google scholar: lookup
      22. Pérez-Fuentes L, Drummond C, Faraudo J, Bastos-González D. Adsorption of Milk Proteins (β-Casein and β-Lactoglobulin) and BSA onto Hydrophobic Surfaces. Materials (Basel) 2017 Aug 2;10(8).
        doi: 10.3390/ma10080893pubmed: 28767100google scholar: lookup
      23. Goncharov NV, Belinskaia DA, Shmurak VI, Terpilowski MA, Jenkins RO, Avdonin PV. Serum Albumin Binding and Esterase Activity: Mechanistic Interactions with Organophosphates. Molecules 2017 Jul 18;22(7).
        doi: 10.3390/molecules22071201pubmed: 28718803google scholar: lookup
      24. Venturini D, de Souza AR, Caracelli I, Morgon NH, da Silva-Filho LC, Ximenes VF. Induction of axial chirality in divanillin by interaction with bovine serum albumin. PLoS One 2017;12(6):e0178597.
        doi: 10.1371/journal.pone.0178597pubmed: 28575123google scholar: lookup
      25. Li C, Huang T, Fu Y, Liu Y, Zhou S, Qi Z, Li C. Interaction of Di-2-pyridylketone 2-pyridine Carboxylic Acid Hydrazone and Its Copper Complex with BSA: Effect on Antitumor Activity as Revealed by Spectroscopic Studies. Molecules 2016 Apr 28;21(5).
        doi: 10.3390/molecules21050563pubmed: 27136517google scholar: lookup
      26. Sekula B, Ciesielska A, Rytczak P, Koziołkiewicz M, Bujacz A. Structural evidence of the species-dependent albumin binding of the modified cyclic phosphatidic acid with cytotoxic properties. Biosci Rep 2016 Jul;36(3).
        doi: 10.1042/BSR20160089pubmed: 27129297google scholar: lookup
      27. Lau EC, Mason DJ, Eichhorst N, Engelder P, Mesa C, Kithsiri Wijeratne EM, Gunaherath GM, Gunatilaka AA, La Clair JJ, Chapman E. Functional chromatographic technique for natural product isolation. Org Biomol Chem 2015 Feb 28;13(8):2255-9.
        doi: 10.1039/c4ob02292kpubmed: 25588099google scholar: lookup
      28. Joksimović N, Petronijević J, Filipović I, Janković N, Ilić B, Stanojković T, Djurić A. Multi-Target Anticancer Activity of Structurally Diverse Schiff Bases: Insights into Cell-Cycle Arrest, DNA Damage, Metabolic Signaling, and Biomolecular Binding. Curr Issues Mol Biol 2026 Jan 1;48(1).
        doi: 10.3390/cimb48010057pubmed: 41614887google scholar: lookup
      29. Duszynski K, Sekula B, Talaj J, Bujacz A. Structural Interactions of β-Lactam Antibiotics with Mammalian Serum Albumins. Int J Mol Sci 2026 Jan 13;27(2).
        doi: 10.3390/ijms27020776pubmed: 41596427google scholar: lookup
      30. Feldman R, Gummin D, Hawi M, Lyneis J, Abourashed E. Can Albumin Trap Salicylate? An In Vitro Exploration of Salicylate Overdose Scenarios. J Med Toxicol 2026 Jan;22(1):29-38.
        doi: 10.1007/s13181-025-01113-5pubmed: 41413367google scholar: lookup
      31. Mansour FR, Elhosary N, Elagamy SH, Barseem A, Kamal AH. Multi spectroscopic investigations with molecular docking and molecular dynamics simulation of the binding mechanism of molnupiravir to bovine serum albumin. BMC Chem 2025 Oct 27;19(1):286.
        doi: 10.1186/s13065-025-01645-5pubmed: 41146332google scholar: lookup
      32. Chatterjee S, Dube A, Majumder SK. Unveiling role of serum albumin in disaggregation and cellular delivery of a near-infrared chlorophyll-based photosensitizer in breast cancer cells. Photochem Photobiol Sci 2025 Aug;24(8):1373-1392.
        doi: 10.1007/s43630-025-00764-1pubmed: 40690194google scholar: lookup
      33. Khatun MH, Sami SA, Mim FS, Kumar P, Islam A, Al Mahamud Rian I, Rahman MA, Riya SI, Lokman M, Mamun A, Haque MA, Yeasmin MS, Rana GMM, Barmon J. Unveiling Pharmacological Promise of Mangifera indica (Haribhanga) Peel Extract: Exploring an Untapped Cultivar Through Biochemical and Computational Approaches. Scientifica (Cairo) 2025;2025:6516268.
        doi: 10.1155/sci5/6516268pubmed: 40225279google scholar: lookup
      34. Dimitrić Marković J, Dimić D, Eichhorn T, Milenković D, Pavićević A, Đikić D, Živković E, Čokić V, Rüffer T, Kaluđerović GN. Ru(II) Complexes with 3,4-Dimethylphenylhydrazine: Exploring In Vitro Anticancer Activity and Protein Affinities. Biomolecules 2025 Feb 28;15(3).
        doi: 10.3390/biom15030350pubmed: 40149886google scholar: lookup
      35. Kasalović MP, Jelača S, Dimić D, Maksimović-Ivanić D, Jevtić VV, Mijatović S, Rüffer T, Kaluđerović GN, Pantelić NĐ. Organic Moiety on Sn(IV) Does Matter for In Vitro Mode of Action: nBu(3)Sn(IV) Compounds with Carboxylato N-Functionalized 2-Quinolones Induce Anoikis-like Cell Death in A375 Cells. Pharmaceutics 2024 Nov 28;16(12).
        doi: 10.3390/pharmaceutics16121529pubmed: 39771508google scholar: lookup
      36. Belinskaia DA, Batalova AA, Voronina PA, Shmurak VI, Vovk MA, Polyanichko AM, Sych TS, Samodurova KV, Antonova VK, Volkova AA, Gerda BA, Jenkins RO, Goncharov NV. Modulation of Albumin Esterase Activity by Warfarin and Diazepam. Int J Mol Sci 2024 Oct 27;25(21).
        doi: 10.3390/ijms252111543pubmed: 39519097google scholar: lookup
      37. Parigger L, Krassnigg A, Hetmann M, Hofmann A, Gruber K, Steinkellner G, Gruber CC. CavitOmiX Drug Discovery: Engineering Antivirals with Enhanced Spectrum and Reduced Side Effects for Arboviral Diseases. Viruses 2024 Jul 24;16(8).
        doi: 10.3390/v16081186pubmed: 39205160google scholar: lookup
      38. Kasalović MP, Dimić D, Jelača S, Maksimović-Ivanić D, Mijatović S, Zmejkovski BB, Schreiner SHF, Rüffer T, Pantelić NĐ, Kaluđerović GN. Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells. Pharmaceuticals (Basel) 2024 Mar 14;17(3).
        doi: 10.3390/ph17030372pubmed: 38543158google scholar: lookup
      39. Alshammari OAO, Maisara S, Alshammari B, Alshammari MR, Rakic V, Dimitrić Marković J, Jevtovic V, Dimić D. Theoretical Insights into Different Complexation Modes of Dioxovanadium(V) Compounds with Pyridoxal Semicarbazone/Thiosemicarbazone/S-Methyl-iso-thiosemicarbazone Ligands. Molecules 2024 Mar 8;29(6).
        doi: 10.3390/molecules29061213pubmed: 38542848google scholar: lookup
      40. Jevtovic V, Alhar MSO, Milenković D, Marković Z, Dimitrić Marković J, Dimić D. Synthesis, Structural Characterization, Cytotoxicity, and Protein/DNA Binding Properties of Pyridoxylidene-Aminoguanidine-Metal (Fe, Co, Zn, Cu) Complexes. Int J Mol Sci 2023 Sep 29;24(19).
        doi: 10.3390/ijms241914745pubmed: 37834192google scholar: lookup