title: Molecular characterization of serine protease inhibitor isoform 3, SmSPI, from Schistosoma mansoni.
abstract: Serine protease inhibitors, known as serpins, are pleiotropic regulators of endogenous and exogenous proteases, and molecule transporters. They have been documented in animals, plants, fungi, bacteria, and viruses; here, we characterize a serpin from the trematode platyhelminth Schistosoma mansoni. At least eight serpins have been found in the genome of S. mansoni, but only two have characterized molecular properties and functions. Here, the function of S. mansoni serpin isoform 3 (SmSPI) was analyzed, using both computational and molecular biological approaches. Phylogenetic analysis showed that SmSPI was closely related to Schistosoma haematobium serpin and Schistosoma japonicum serpin B10. Structure determined in silico confirmed that SmSPI belonged to the serpin superfamily, containing nine α-helices, three β-sheets, and a reactive central loop. SmSPI was highly expressed in schistosomules, predominantly in the head gland, and in adult male and female with intensive accumulation on the spines, which suggests that it may have a role in facilitating intradermal and intravenous survival. Recombinant SmSPI was overexpressed in Escherichia coli; the recombinant protein was of the same size (46 kDa) as the native protein. Immunological analysis suggested that mice infected with S. mansoni responded to rSmSPI at 8 weeks postinfection (wpi) but not earlier. The inhibitory activity of rSmSPI was specific to chymotrypsin but not trypsin, neutrophil elastase, and porcine pancreatic elastase. Elucidating the biological and physiological functions of SmSPI as well as other serpins will lead to further understanding of host-parasite interaction machinery that may provide novel strategies to prevent and control schistosomiasis in the future.
authors.affiliation: Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Pattarakul
authors.initials: P
authors.lastname: Pakchotanon
authors.affiliation: Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.|Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Patamaporn
authors.initials: P
authors.lastname: Molee
authors.affiliation: Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Supaporn
authors.initials: S
authors.lastname: Nuamtanong
authors.affiliation: Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Yanin
authors.initials: Y
authors.lastname: Limpanont
authors.affiliation: Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Phiraphol
authors.initials: P
authors.lastname: Chusongsang
authors.affiliation: Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Jareemate
authors.initials: J
authors.lastname: Limsomboon
authors.affiliation: Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Yupa
authors.initials: Y
authors.lastname: Chusongsang
authors.affiliation: Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Santi
authors.initials: S
authors.lastname: Maneewatchararangsri
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Urai
authors.initials: U
authors.lastname: Chaisri
authors.affiliation: Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand. poom.adi@mahidol.ac.th.|Center of Excellence for Antibody Research (CEAR), Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand. poom.adi@mahidol.ac.th.
authors.forename: Poom
authors.initials: P
authors.lastname: Adisakwattana
mesh_terms: D000818:Animals; D005260:Female; D006790:Host-Parasite Interactions / Q000187:drug effects; D008297:Male; D051379:Mice; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012550:Schistosoma mansoni / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000469:parasitology; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D015843:Serpins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D013552:Swine
chemical_list: D020033:Protein Isoforms; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D015843:Serpins
keywords: Chymotrypsin; In silico structure; Schistosoma mansoni; Schistosomule; Serine protease inhibitor (serpin)