title: A functionally atypical amidating enzyme from the human parasite Schistosoma mansoni.
abstract: Many neuropeptide transmitters require the presence of a carboxy-terminal alpha-amide group for biological activity. Amidation requires conversion of a glycine-extended peptide intermediate into a C-terminally amidated product. This post-translational modification depends on the sequential action of two enzymes (peptidylglycine alpha-hydroxylating monooxygenase or PHM, and peptidyl-alpha-hydroxyglycine alpha-amidating lyase or PAL) that in most eukaryotes are expressed as separate domains of a single protein (peptidylglycine alpha-amidating monooxygenase or PAM). We identified a cDNA encoding PHM in the human parasite Schistosoma mansoni. Transient expression of schistosome PHM (smPHM) revealed functional properties that are different from other PHM proteins; smPHM displays a lower pH-optimum and, when expressed in mammalian cells, is heavily N-glycosylated. In adult worms, PHM is found in the trans-Golgi network and secretory vesicles of both central and peripheral nerves. The widespread occurrence of PHM in the nervous system confirms the important role of amidated neuropeptides in these parasitic flatworms. The differences between schistosome and mammalian PHM suggest that it could be a target for new chemotherapeutics.
authors.affiliation: Parasitology Research Group, School of Biology and Biochemistry, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: Gunnar R
authors.initials: GR
authors.lastname: Mair
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Niciu
authors.forename: Michael T
authors.initials: MT
authors.lastname: Stewart
authors.forename: Gerry
authors.initials: G
authors.lastname: Brennan
authors.forename: Hanan
authors.initials: H
authors.lastname: Omar
authors.forename: David W
authors.initials: DW
authors.lastname: Halton
authors.forename: Richard
authors.initials: R
authors.lastname: Mains
authors.forename: Betty A
authors.initials: BA
authors.lastname: Eipper
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Maule
authors.forename: Tim A
authors.initials: TA
authors.lastname: Day
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology; D012550:Schistosoma mansoni / Q000033:anatomy & histology / Q000201:enzymology*; D016415:Sequence Alignment
chemical_list: D018076:DNA, Complementary; D009097:Multienzyme Complexes; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase