title: Towards an understanding of the function of the phytochelatin synthase of Schistosoma mansoni.
abstract: Phytochelatin synthase (PCS) is a protease-like enzyme that catalyzes the production of metal chelating peptides, the phytochelatins, from glutathione (GSH). In plants, algae, and fungi phytochelatin production is important for metal tolerance and detoxification. PCS proteins also function in xenobiotic metabolism by processing GSH S-conjugates. The aim of the present study is to elucidate the role of PCS in the parasitic worm Schistosoma mansoni. Recombinant S. mansoni PCS proteins expressed in bacteria could both synthesize phytochelatins and hydrolyze various GSH S-conjugates. We found that both the N-truncated protein and the N- and C-terminal truncated form of the enzyme (corresponding to only the catalytic domain) work through a thiol-dependant and, notably, metal-independent mechanism for both transpeptidase (phytochelatin synthesis) and peptidase (hydrolysis of GSH S-conjugates) activities. PCS transcript abundance was increased by metals and xenobiotics in cultured adult worms. In addition, these treatments were found to increase transcript abundance of other enzymes involved in GSH metabolism. Highest levels of PCS transcripts were identified in the esophageal gland of adult worms. Taken together, these results suggest that S. mansoni PCS participates in both metal homoeostasis and xenobiotic metabolism rather than metal detoxification as previously suggested and that the enzyme may be part of a global stress response in the worm. Because humans do not have PCS, this enzyme is of particular interest as a drug target for schistosomiasis.
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors: Coraline
authors: C
authors: Rigouin
authors: Elyse
authors: E
authors: Nylin
authors: Alexis A
authors: AA
authors: Cogswell
authors: Dirk
authors: D
authors: Schaumlöffel
authors: Dirk
authors: D
authors: Dobritzsch
authors: David L
authors: DL
authors: Williams
mesh_terms: D019881:Aminoacyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D005978:Glutathione / Q000378:metabolism; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008670:Metals / Q000378:metabolism; D010458:Peptidyl Transferases / Q000235:genetics / Q000378:metabolism; D054811:Phytochelatins / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012550:Schistosoma mansoni / Q000201:enzymology* / Q000502:physiology*; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D008670:Metals; D011994:Recombinant Proteins; D015262:Xenobiotics; D054811:Phytochelatins; D019881:Aminoacyltransferases; D010458:Peptidyl Transferases; C093784:glutathione gamma-glutamylcysteinyltransferase; D006867:Hydrolases; D005978:Glutathione
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