Bothrops moojeni myotoxin-II, a Lys49-phospholipase A2 homologue: an example of function versatility of snake venom proteins.
MjTX-II, a myotoxic phospholipase A(2) (PLA(2)) homologue from Bothrops moojeni venom, was functionally and structurally characterized. The MjTX-II characterization included: (i) functional characterization (antitumoral, antimicrobial and antiparasitic effects); (ii) effects of structural modifications by 4-bromophenacyl bromide (BPB), cyanogen bromide (CNBr), acetic anhydride and 2-nitrobenzenesulphonyl fluoride (NBSF); (iii) enzymatic characterization: inhibition by low molecular weight heparin and EDTA; and (iv) molecular characterization: cDNA sequence and molecular structure prediction. The results demonstrated that MjTX-II displayed antimicrobial activity by growth inhibition against Escherichia coli and Candida albicans, antitumoral activity against Erlich ascitic tumor (EAT), human breast adenocarcinoma (SK-BR-3) and human T leukemia cells (JURKAT) and antiparasitic effects against Schistosoma mansoni and Leishmania spp., which makes MjTX-II a promising molecular model for future therapeutic applications, as well as other multifunctional homologous Lys49-PLA(2)s or even derived peptides. This work provides useful insights into the structural determinants of the action of Lys49-PLA(2) homologues and, together with additional strategies, supports the concept of the presence of others "bioactive sites" distinct from the catalytic site in snake venom myotoxic PLA(2)s.
Stábeli
Rodrigo G
RG
Instituto de Pesquisas em Patologias Tropicais, IPEPATRO, Universidade Federal de Rondonia, UNIR-RO, Brazil.
Amui
Saulo F
SF
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, USP, Ribeirão Preto-SP, Brazil.
Sant'Ana
Carolina D
CD
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, USP, Ribeirão Preto-SP, Brazil.
Pires
Matheus G
MG
Instituto de Pesquisas em Patologias Tropicais, IPEPATRO, Universidade Federal de Rondonia, UNIR-RO, Brazil.
Nomizo
Auro
A
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, USP, Ribeirão Preto-SP, Brazil.
Monteiro
Marta C
MC
Universidade Estadual do Centro-Oeste/UNICENTRO, Guarapuava-PR, Brazil.
Romão
Pedro R T
PRT
Laboratório de Imunoparasitologia, UNISUL, Tubarão-SC, Brazil.
Guerra-Sá
Renata
R
Laboratório de Bioquímica e Biologia Molecular-Departamento de Ciências Biológicas, UFOP, Ouro Preto-MG, Brazil.
Vieira
Carlos A
CA
Departamento de Bioquímica e Imunologia, FMRP, USP, Ribeirão Preto-SP, Brazil.
Giglio
José R
JR
Departamento de Bioquímica e Imunologia, FMRP, USP, Ribeirão Preto-SP, Brazil.
Fontes
Marcos R M
MRM
Departamento de Física e Biofísica, IB, UNESP, Botucatu-SP, Brazil.
Soares
Andreimar M
AM
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, USP, Ribeirão Preto-SP, Brazil. Electronic address: andreims@fcfrp.usp.br.
D000089:Acetic Anhydrides / Q000737:chemistry; D000098:Acetophenones / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017837:Bothrops; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D003402:Creatine Kinase / Q000097:blood; D003488:Cyanogen Bromide / Q000737:chemistry; D004487:Edema / Q000139:chemically induced; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D019169:Jurkat Cells; D007891:Leishmania / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D009578:Nitrobenzenes / Q000737:chemistry; D010741:Phospholipases A / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects / Q000472:pathogenicity; D017422:Sequence Analysis, DNA
C427238:2-nitrobenzenesulfonyl fluoride; D000089:Acetic Anhydrides; D000098:Acetophenones; D009498:Neurotoxins; D009578:Nitrobenzenes; C031800:acetic anhydride; D003402:Creatine Kinase; C114084:myotoxin II, Bothrops moojeni; D010741:Phospholipases A; D003488:Cyanogen Bromide; C006821:4-bromophenacyl bromide