Kinetic characterization of methionine gamma-lyases from the enteric protozoan parasite Entamoeba histolytica against physiological substrates and trifluoromethionine, a promising lead compound against amoebiasis

The FEBS Journal
Dan SatoT Nozaki

Abstract

Methionine gamma-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 alpha-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 addition, the physiological significance of the presence of two MGL isozymes in these protists remains unclear. In this study, we compared kinetic parameters of the wild-type and mutants, engineered by site-directed mutagenesis, of the two MGL isotypes from En. histolytica (EhMGL1 and EhMGL2) for various potential substrates and TFM. Intracellular concentrations of l-Met and l-Cys suggested that these SAAs are predominantly metabolized ...Continue Reading

References

May 1, 1975·Journal of Bacteriology·F ColombaniH de Robichon-Szulmajster
Nov 1, 1991·The Biochemical Journal·B C Lockwood, G H Coombs
Feb 1, 1966·Canadian Journal of Microbiology·W A Zygmunt, P A Tavormina
May 1, 1984·Analytical Biochemistry·T NakayamaK Soda
Mar 1, 1983·Biochemical Pharmacology·T A Alston, H J Bright
Jul 1, 1995·The Journal of Eukaryotic Microbiology·T Bakker-GrunwaldG Klein
Sep 3, 1998·Applied and Environmental Microbiology·B Dias, B Weimer
Nov 18, 2000·Infection and Immunity·M YoshimuraT Koga
Jan 9, 2001·Clinical Microbiology Reviews·P Upcroft, J A Upcroft
Feb 24, 2001·Bioscience, Biotechnology, and Biochemistry·H InoueH Tanaka
Apr 12, 2002·Biochemical and Biophysical Research Communications·Mamiko YoshimuraToshihiko Koga
Mar 28, 2003·Lancet·Samuel L Stanley
Oct 31, 2003·Cancer Treatment Reviews·E CellarierP Chollet
Mar 5, 2004·Cellular and Molecular Life Sciences : CMLS·H Jakubowski
Jun 16, 2005·Experimental Parasitology·Iain J Anderson, Brendan J Loftus
Oct 19, 2005·Advances in Parasitology·Tomoyoshi NozakiMasaharu Tokoro
Mar 3, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·D V MamaevaT V Demidkina
Mar 30, 2006·Molecular and Biochemical Parasitology·Carol A GilchristWilliam A Petri
May 17, 2006·The Journal of Nutrition·John T Brosnan, Margaret E Brosnan
Oct 3, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Dan SatoShigeharu Harada
Oct 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Fabrice RébeilléStéphane Ravanel
Dec 8, 2007·Advances in Parasitology·C G ClarkN Hall

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Citations

Feb 11, 2010·Applied Microbiology and Biotechnology·Ashraf S El-Sayed
Jun 17, 2011·The Journal of Antimicrobial Chemotherapy·Gil M PenuliarTomoyoshi Nozaki
Nov 24, 2011·The Journal of Antimicrobial Chemotherapy·Gil M PenuliarTomoyoshi Nozaki
Aug 6, 2008·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Dan SatoTomoyoshi Nozaki
Jul 13, 2012·Bioscience, Biotechnology, and Biochemistry·Mitsuki FukumotoKenji Inagaki
Nov 17, 2009·International Journal of Antimicrobial Agents·Dan SatoTomoyoshi Nozaki
Nov 26, 2009·Molecular and Biochemical Parasitology·Afzal HusainTomoyoshi Nozaki
Mar 23, 2017·Protein Science : a Publication of the Protein Society·Dan SatoShigeharu Harada
Dec 10, 2013·Biochimie·Takashi Makiuchi, Tomoyoshi Nozaki
Jun 5, 2019·Analytical Biochemistry·Shiro KatoTadao Oikawa
May 4, 2021·Frontiers in Cellular and Infection Microbiology·Suneeta DeviSamudrala Gourinath

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