title: BmajPLA2-II, a basic Lys49-phospholipase A2homologue from Bothrops marajoensis snake venom with parasiticidal potential.
abstract: Snake venoms contain various proteins, especially phospholipases A2(PLA2s), which present potential applications in diverse areas of health and medicine. In this study, a new basic PLA2from Bothrops marajoensis with parasiticidal activity was purified and characterized biochemically and biologically. B. marajoensis venom was fractionated through cation exchange followed by reverse phase chromatographies. The isolated toxin, BmajPLA2-II, was structurally characterized with MALDI-TOF (Matrix-assisted laser desorption/ionization-time of flight) mass spectrometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by two-dimensional electrophoresis, partial amino acid sequencing, an enzymatic activity assay, circular dichroism, and dynamic light scattering assays. These structural characterization tests presented BmajPLA2-II as a basic Lys49 PLA2homologue, compatible with other basic snake venom PLA2s (svPLA2), with a tendency to form aggregations. The in vitro anti-parasitic potential of B. marajoensis venom and of BmajPLA2-II was evaluated against Leishmania infantum promastigotes and Trypanosoma cruzi epimastigotes, showing significant activity at a concentration of 100μg/mL. The venom and BmajPLA2-II presented IC50of 0.14±0.08 and 6.41±0.64μg/mL, respectively, against intraerythrocytic forms of Plasmodium falciparum with CC50cytotoxicity values against HepG2 cells of 43.64±7.94 and >150μg/mL, respectively. The biotechnological potential of these substances in relation to leishmaniasis, Chagas disease and malaria should be more deeply investigated.
authors.affiliation: Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil.
authors.forename: Amy N
authors.initials: AN
authors.lastname: Grabner
authors.affiliation: Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil; Centro para el Desarrollo de la Investigación Científica, CEDIC, Asunción, Paraguay.
authors.forename: Jorge
authors.initials: J
authors.lastname: Alfonso
authors.affiliation: Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil.
authors.forename: Anderson M
authors.initials: AM
authors.lastname: Kayano
authors.affiliation: Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil.
authors.forename: Leandro S
authors.initials: LS
authors.lastname: Moreira-Dill
authors.affiliation: Laboratório da Plataforma de Bioensaios de Malária e Leishmaniose, Fiocruz Rondônia, Porto Velho-RO, Brazil.
authors.forename: Ana Paula de A
authors.initials: APA
authors.lastname: Dos Santos
authors.affiliation: Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil.
authors.forename: Cleópatra A S
authors.initials: CAS
authors.lastname: Caldeira
authors.affiliation: Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil.
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Sobrinho
authors.affiliation: Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil; Centro para el Desarrollo de la Investigación Científica, CEDIC, Asunción, Paraguay.
authors.forename: Ana
authors.initials: A
authors.lastname: Gómez
authors.affiliation: Faculdade São Lucas, FSL, Porto Velho-RO, Brazil.
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Grabner
authors.affiliation: Departamento de Física e Biofísica, Universidade Estadual Paulista, UNESP, Botucatu-SP, Brazil.
authors.forename: Fabio F
authors.initials: FF
authors.lastname: Cardoso
authors.affiliation: Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil.
authors.forename: Juliana Pavan
authors.initials: JP
authors.lastname: Zuliani
authors.affiliation: Departamento de Física e Biofísica, Universidade Estadual Paulista, UNESP, Botucatu-SP, Brazil.
authors.forename: Marcos R M
authors.initials: MRM
authors.lastname: Fontes
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, Brazil.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Pimenta
authors.affiliation: Centro para el Desarrollo de la Investigación Científica, CEDIC, Asunción, Paraguay.
authors.forename: Celeste Vega
authors.initials: CV
authors.lastname: Gómez
authors.affiliation: Laboratório da Plataforma de Bioensaios de Malária e Leishmaniose, Fiocruz Rondônia, Porto Velho-RO, Brazil.
authors.forename: Carolina B G
authors.initials: CBG
authors.lastname: Teles
authors.affiliation: Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil; Faculdade São Lucas, FSL, Porto Velho-RO, Brazil.
authors.forename: Andreimar M
authors.initials: AM
authors.lastname: Soares
authors.affiliation: Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, FIOCRUZ, Fiocruz Rondônia, Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho-RO, Brazil. Electronic address: calderon@fiocruz.br.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Calderon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017837:Bothrops; D003435:Crotalid Venoms / Q000201:enzymology*; D054467:Phospholipases A2 / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D014357:Trypsin / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D003435:Crotalid Venoms; D054467:Phospholipases A2; D014357:Trypsin
keywords: Bothrops marajoensis; Chagas disease; Leishmaniasis; Malaria; Phospholipase A(2); Snake venoms