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Báo cáo khoa học: Kinetic characterization of methionine c-lyases from the enteric protozoan parasite Entamoeba histolytica against physiological substrates and trifluoromethionine, a promising lead compound against amoebiasis

Methioninec-lyase (MGL) (EC 4.4.1.11), which is present in certain lin-eages of bacteria, plants, and protozoa but missing in mammals, catalyzes the single-step degradation of sulfur-containing amino acids (SAAs) to a-keto acids, ammonia, and thiol compounds. | ễFEBS Journal Kinetic characterization of methionine c-lyases from the enteric protozoan parasite Entamoeba histolytica against physiological substrates and trifluoromethionine a promising lead compound against amoebiasis Dan Sato1 z Wataru Yamagata2 Shigeharu Harada2 and Tomoyoshi Nozaki1 1 Department of Parasitology Gunma University Graduate Schoolof Medicine Japan 2 Department of Applied Biology Graduate Schoolof Science and Technology Kyoto Institute of Technology Japan Keywords amoebiasis methionine y-lyase site-directed mutagenesis sulfur-containing amino acid trifluoromethionine Correspondence T. Nozaki Department of Parasitology Gunma University Graduate Schoolof Medicine 3-39-22 Showa-machi Maebashi Gunma 371-8511 Japan Fax 81 27 220 8020 Tel 81 27 220 8025 E-mail nozaki@med.gunma-u.ac.jp Website http parasite.dept.med.gunma-u. ac.jp Enozaki_lab.html Present address Institute for Advanced Biosciences Keio University Tsuruoka Yamagata Japan Database Nucleotide sequence data are available in the DDBJ EMBL GenBank databases under the accession numbers AB094499 EhMGL1 and AB094500 EhMGL2 Received 29 August 2007 revised 13 November 2007 accepted 4 December 2007 doi 10.1111 j.1742-4658.2007.06221.x Methionine y-lyase MGL EC 4.4.1.11 which is present in certain lineages of bacteria plants and protozoa but missing in mammals catalyzes the single-step degradation of sulfur-containing amino acids SAAs to a-keto acids ammonia and thiol compounds. In contrast to other organisms possessing MGL anaerobic parasitic protists namely Entamoeba histolytica and Trichomonas vaginalis harbor a pair of MGL isozymes. The enteric protozoon En. histolytica shows various unique aspects in its metabolism particularly degradation of SAAs. Trifluoromethionine TFM a halogenated analog of Met has been exploited as a therapeutic agent against cancer as well as against infections by protozoan organisms and periodontal bacteria. However its mechanism of action remains poorly understood. In