Antiviral and antiparasite properties of an L-amino acid oxidase from the snake Bothrops jararaca: cloning and identification of a complete cDNA sequence.
L-Amino acid oxidases (LAAOs, EC 1.4.3.2) are flavoenzymes that catalyze the stereospecific oxidative deamination of an L-amino acid substrate to the corresponding alpha-ketoacid with hydrogen peroxide and ammonia production. The present work describes the first report on the antiviral (Dengue virus) and antiprotozoal (trypanocidal and leishmanicide) activities of a Bothrops jararaca L-amino acid oxidase (BjarLAAO-I) and identify its cDNA sequence. Antiparasite effects were inhibited by catalase, suggesting that they are mediated by H2O2 production. Cells infected with DENV-3 virus previously treated with BjarLAAO-I, showed a decrease in viral titer (13-83-fold) when compared with cells infected with untreated viruses. Untreated and treated promastigotes (T. cruzi and L. amazonensis) were observed by transmission electron microscopy with different degrees of damage. Its complete cDNA sequence, with 1452 bp, encoded an open reading frame of 484 amino acid residues with a theoretical molecular weight and pI of 54,771.8 and 5.7, respectively. The cDNA-deduced amino acid sequence of BjarLAAO shows high identity to LAAOs from other snake venoms. Further investigations will be focused on the related molecular and functional correlation of these enzymes. Such a study should provide valuable information for the therapeutic development of new generations of microbicidal drugs.
Sant'Ana
Carolina D
CD
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, FCFRP-USP, Ribeirão Preto-SP, Brazil.
Menaldo
Danilo L
DL
Costa
Tássia R
TR
Godoy
Harryson
H
Muller
Vanessa D M
VD
Aquino
Victor H
VH
Albuquerque
Sérgio
S
Sampaio
Suely V
SV
Monteiro
Marta C
MC
Stábeli
Rodrigo G
RG
Soares
Andreimar M
AM
D000330:Aedes; D000595:Amino Acid Sequence; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D017837:Bothrops; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D003435:Crotalid Venoms / Q000737:chemistry*; D018076:DNA, Complementary / Q000235:genetics; D003716:Dengue Virus / Q000187:drug effects; D050830:L-Amino Acid Oxidase / Q000235:genetics / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects; D008969:Molecular Sequence Data; D014349:Trypanosoma cruzi / Q000187:drug effects
D000981:Antiprotozoal Agents; D000998:Antiviral Agents; D003435:Crotalid Venoms; D018076:DNA, Complementary; D050830:L-Amino Acid Oxidase