Molecular and Cellular Biochemistry

, Volume 404, Issue 1–2, pp 97–102 | Cite as

Functional and structural changes of human erythrocyte catalase induced by cimetidine: proposed model of binding

  • Fatemeh Yazdi
  • Dariush Minai-Tehrani
  • Mahboubeh Jahngirvand
  • Ali Almasirad
  • Zahra Mousavi
  • Masoudeh Masoud
  • Hamidreza Mollasalehi


In erythrocyte, catalase plays an important role to protect cells from hydrogen peroxide toxicity. Hydrogen peroxide is a byproduct compound which is produced during metabolic pathway of cells. Cimetidine, a histamine H2 receptor antagonist, is used for gastrointestinal tract diseases and prevents the extra release of gastric acid. In this study, the effect of cimetidine on the activity of human erythrocyte catalase was investigated. Erythrocytes were broken by hypotonic solution. The supernatant was used for catalase assay and kinetics study. Lineweaver–Burk plot was performed to determine the type of inhibition. The kinetics data revealed that cimetidine inhibited the catalase activity by mixed inhibition. The IC50 (1.54 μM) and Ki (0.45 μM) values of cimetidine determined that the drug was bound to the enzyme with high affinity. Circular dichroism and fluorescence measurement showed that the binding of cimetidine to the enzyme affected the content of secondary structure of the enzyme as well as its conformational changes. Docking studies were carried out to detect the site in which the drug was bound to the enzyme. Molecular modeling and energy calculation of the binding showed that the cyanoguanidine group of the drug connected to Asp59 via two hydrogen bonds, while the imidazole group of the drug interacted with Phe64 in the enzyme by a hydrophobic interaction. In conclusion, cimetidine could bind to human erythrocyte catalase, and its interaction caused functional and conformational changes in the enzyme.


Erythrocyte Enzyme Inhibition Drug Model of binding 


  1. 1.
    Butterfield DA, Lauderback CM (2002) Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress. Free Radic Biol Med 32:1050–1060CrossRefPubMedGoogle Scholar
  2. 2.
    Howe CJ, LaHair MM, McCubrey JA, Franklin RA (2004) Redox regulation of the CaM-kinases. J Biol Chem 279:44573–44581CrossRefPubMedGoogle Scholar
  3. 3.
    Huang X, Moir RD, Tanzi RE, Bush AI, Rogers JT (2004) Redox-active metals, oxidative stress, and Alzheimer’s disease pathology. Ann N Y Acad Sci 1012:153–163CrossRefPubMedGoogle Scholar
  4. 4.
    Nagababu E, Chrest FJ, Rifkind JM (2003) Hydrogen-peroxide-induced heme degradation in red blood cells: the protective roles of catalase and glutathione peroxidise. Biochim Biophys Acta 1620:211–217CrossRefPubMedGoogle Scholar
  5. 5.
    Giulivi C, Hochstein P, Davies KJ (1994) Hydrogen peroxide production by red blood cells. Free Radic Biol Med 16:123–129CrossRefPubMedGoogle Scholar
  6. 6.
    Putnam CD, Arvai AS, Bourne Y, Tainer JA (2000) Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism. J Mol Biol 296:295–309CrossRefPubMedGoogle Scholar
  7. 7.
    Aksoy Y, Balk M, Ogus H, Ozer N (2014) The mechanism of inhibition of human erythrocyte catalase by azide. Turk J Biol 28:65–70Google Scholar
  8. 8.
    Hokama Y, Yanagihara E (1971) The reversible inhibition of catalase activity by nucleotides and its possible relationship to mouse liver catalase depression induced by biological substances. Cancer Res 31:2018–2025PubMedGoogle Scholar
  9. 9.
    Masoud M, Ebrahimi F, Minai-Tehrani D (2014) Effect of cimetidine on catalase activity of Pseudomonas aeruginosa: a suggested mechanism of action. J Mol Microbiol Biotechnol 24:196–201CrossRefPubMedGoogle Scholar
  10. 10.
    Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity. J Comput Chem 30:2785–2791CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Laskowski RA, Thornton JM, Wallace AC (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8:127–134CrossRefPubMedGoogle Scholar
  12. 12.
    Altikat S, Coban A, Ciftci M, Ozdemir H (2006) In vitro effects of some drugs on catalase purified from human skin. J Enzym Inhib Med Chem 21:231–234CrossRefGoogle Scholar
  13. 13.
    Minai-Tehrani D, Minoui S, Sepehre M, Sharif-Khodai Z, Aavani T (2009) Inhibitory effect of codeine on sucrase activity. Drug Metab Lett 3:58–60CrossRefPubMedGoogle Scholar
  14. 14.
    Minai-Tehrani D, Masoudnia A, Alavi S, Osmani R, Lotfi L, Asghari M, Pirsalehi M, Sobhani-Damavandifar Z (2012) Interaction of methocarbamol and yeast sucrase induces an inhibition. Drug Metab Drug Interact 27:225–228Google Scholar
  15. 15.
    Kondo T, Suzuki Y, Kitano T, Iwai K, Watanabe M, Umehara H, Daido N, Domae N, Tashima M, Uchiyama T, Okazaki T (2002) Vesnarinone causes oxidative damage by inhibiting catalase function through ceramide action in myeloid cell apoptosis. Mol Pharmacol 61:620–627CrossRefPubMedGoogle Scholar
  16. 16.
    Metaye T, Mettey Y, Vierfond JM, Lalegerie P (1988) Comparative inhibition of human alkaline phosphatase and diamine oxidase by bromo-levamisole, cimetidine and various derivatives. Biochem Pharmacol 37:4263–4268CrossRefPubMedGoogle Scholar
  17. 17.
    Minai-Tehrani D, Khodai S, Aminnaseri S, Minoui S, Sobhani-Damavadifar Z, Alavi S, Osmani R, Ahmadi S (2011) Inhibition of renal alkaline phosphatase by cimetidine. Drug Metab Lett 5:197–201CrossRefPubMedGoogle Scholar
  18. 18.
    Minai-Tehrani D, Ghaffari M, Sobhani-Damavandifar Z, Minoui S, Alavi S, Osmani R, Ahmadi S (2012) Ranitidine induces inhibition and structural changes in sucrase. J Enzym Inhib Med Chem 27:553–557CrossRefGoogle Scholar
  19. 19.
    Minai-Tehrani D, Fooladi N, Minoui S, Sobhani-Damavandifar Z, Aavani T, Heydarzadeh S, Attar F, Ghaffari M, Nazem H (2010) Structural changes and inhibition of sucrase after binding of scopolamine. Eur J Pharmacol 635:23–26CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Fatemeh Yazdi
    • 1
  • Dariush Minai-Tehrani
    • 2
  • Mahboubeh Jahngirvand
    • 3
  • Ali Almasirad
    • 1
  • Zahra Mousavi
    • 1
  • Masoudeh Masoud
    • 2
  • Hamidreza Mollasalehi
    • 4
  1. 1.Pharmaceutical Sciences BranchIslamic Azad UniversityTehranIran
  2. 2.BioResearch Lab, Faculty of Biological SciencesShahid Beheshti University, G.C.TehranIran
  3. 3.Biochemistry Department, Science and Research BranchIslamic Azad UniversityShirazIran
  4. 4.Protein Research CenterShahid Beheshti University, G.C.TehranIran

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