caa a22 4500 606233555 CHVBK 20210128101232.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s11010-015-2369-3 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2369-3 Functional and structural changes of human erythrocyte catalase induced by cimetidine: proposed model of binding [Elektronische Daten] [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 (1.54μM) and Ki (0.45μM) 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. Springer Science+Business Media New York, 2015 Erythrocyte nationallicence Enzyme nationallicence Inhibition nationallicence Drug nationallicence Model of binding nationallicence Yazdi Fatemeh Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran aut Minai-Tehrani Dariush BioResearch Lab, Faculty of Biological Sciences, Shahid Beheshti University, G.C., Tehran, Iran aut Jahngirvand Mahboubeh Biochemistry Department, Science and Research Branch, Islamic Azad University, Shiraz, Iran aut Almasirad Ali Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran aut Mousavi Zahra Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran aut Masoud Masoudeh BioResearch Lab, Faculty of Biological Sciences, Shahid Beheshti University, G.C., Tehran, Iran aut Mollasalehi Hamidreza Protein Research Center, Shahid Beheshti University, G.C., Tehran, Iran aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 97-102 0300-8177 404:1-2<97 2015 404 11010 https://doi.org/10.1007/s11010-015-2369-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 brief-communication jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2369-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yazdi Fatemeh Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran aut NATIONALLICENCE 700 1- Minai-Tehrani Dariush BioResearch Lab, Faculty of Biological Sciences, Shahid Beheshti University, G.C., Tehran, Iran aut NATIONALLICENCE 700 1- Jahngirvand Mahboubeh Biochemistry Department, Science and Research Branch, Islamic Azad University, Shiraz, Iran aut NATIONALLICENCE 700 1- Almasirad Ali Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran aut NATIONALLICENCE 700 1- Mousavi Zahra Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran aut NATIONALLICENCE 700 1- Masoud Masoudeh BioResearch Lab, Faculty of Biological Sciences, Shahid Beheshti University, G.C., Tehran, Iran aut NATIONALLICENCE 700 1- Mollasalehi Hamidreza Protein Research Center, Shahid Beheshti University, G.C., Tehran, Iran aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 97-102 0300-8177 404:1-2<97 2015 404 11010