title: Effect of cimetidine on catalase activity of Pseudomonas aeruginosa: a suggested mechanism of action.
abstract: Catalase is an important enzyme for the degradation of hydrogen peroxide in cells. Bacteria have potent catalase to deal with H2O2 in their medium culture. Any chemicals that inhibit catalase activity can be harmful for cells. Histamine H2 antagonist drugs such as cimetidine and ranitidine are used for the treatment of gastrointestinal tract disorders. The present results showed that cimetidine could inhibit the catalase activity of Pseudomonas aeruginosa in a competitive inhibition. The determination of IC50 value and Ki (6.5 μM) of cimetidine demonstrated that the enzyme binds to the drug with high affinity. Binding of the drug to the enzyme was pH-dependent and no binding was observed at basic pH (>9) and acidic pH (<6). Moreover, the imidazole ring and cyanoguanidine group of cimetidine may play an important role in inhibition by binding to Fe in heme group and glutamic acid 51 residue on the enzyme, respectively. Ranitidine had no effect on the catalase activity.
authors.affiliation: BioResearch Lab, Faculty of Biological Sciences, Shahid Beheshti University, GC, Tehran, Iran.
authors.forename: Masoudeh
authors.initials: M
authors.lastname: Masoud
authors.forename: Farnoosh
authors.initials: F
authors.lastname: Ebrahimi
authors.forename: Dariush
authors.initials: D
authors.lastname: Minai-Tehrani
mesh_terms: D001665:Binding Sites; D002374:Catalase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002927:Cimetidine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D002927:Cimetidine; D002374:Catalase