title: Structural and evolutionary insights into endogenous alpha-phospholipase A2 inhibitors of Latin American pit vipers.
abstract: Phospholipases A2 are major components of snake venoms (svPLA2s) and are able to induce multiple local and systemic deleterious effects upon envenomation. Several snake species are provided with svPLA2 inhibitors (sbPLIs) in their circulating blood, which confer a natural resistance against the toxic components of homologous and heterologous venoms. The sbPLIs belong to any of three structural classes named α, β and γ. In the present study, we identified, characterized and performed structural and evolutionary analyses of sbαPLIs transcripts and the encoded proteins, in the most common Latin American pit vipers belonging to Crotalus, Bothrops and Lachesis genera. Mutation data indicated that sbαPLIs from Latin American snakes might have evolved in an accelerated manner, similarly to that reported for sbαPLIs from Asian snakes, and possibly co-evoluted with svPLA2s in response to the diversity of target enzymes. The importance of sbαPLI trimerization for the effective binding and inhibition of acidic svPLA2s is discussed and conserved cationic residues located at the central pore of the inhibitor trimer are suggested to be a significant part of the binding site of sbαPLIs to acidic svPLA2s. Our data contribute to the current body of knowledge on the structural and evolutionary characteristics of sbPLIs, in general, and may assist in the future development of selective inhibitors for secretory PLA2 from several sources.
authors.affiliation: Fundação Ezequiel Dias (FUNED), Belo Horizonte, MG, Brazil; Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Maria Inácia
authors.initials: MI
authors.lastname: Estevão-Costa
authors.affiliation: Departamento de Física e Biofísica, Instituto de Biociências, Universidade Estadual Paulista (UNESP), Botucatu, SP, Brazil.
authors.forename: Carlos Alexandre H
authors.initials: CA
authors.lastname: Fernandes
authors.affiliation: Fundação Ezequiel Dias (FUNED), Belo Horizonte, MG, Brazil.
authors.forename: Maurício de Alvarenga
authors.initials: Mde A
authors.lastname: Mudadu
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Glória Regina
authors.initials: GR
authors.lastname: Franco
authors.affiliation: Departamento de Física e Biofísica, Instituto de Biociências, Universidade Estadual Paulista (UNESP), Botucatu, SP, Brazil. Electronic address: fontes@ibb.unesp.br.
authors.forename: Marcos Roberto M
authors.initials: MR
authors.lastname: Fontes
authors.affiliation: Fundação Ezequiel Dias (FUNED), Belo Horizonte, MG, Brazil. Electronic address: consuelo.latorre@funed.mg.gov.br.
authors.forename: Consuelo Latorre
authors.initials: CL
authors.lastname: Fortes-Dias
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017837:Bothrops / Q000235:genetics / Q000378:metabolism*; D001938:Brazil; D016384:Consensus Sequence; D017124:Conserved Sequence; D003435:Crotalid Venoms / Q000378:metabolism*; D017839:Crotalus / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D059645:Mutation Rate; D064801:Phospholipase A2 Inhibitors / Q000737:chemistry / Q000378:metabolism*; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D030162:Reptilian Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017819:Viperidae / Q000235:genetics / Q000378:metabolism*
chemical_list: D003435:Crotalid Venoms; D064801:Phospholipase A2 Inhibitors; D011994:Recombinant Proteins; D030162:Reptilian Proteins; D054497:Phospholipases A2, Secretory
keywords: PLA(2); PLI; Phospholipase A(2); Phospholipase A(2) inhibitor; Snake; Viperidae