Author(s): Toyama, Daniela de Oliveira ; Gaeta, Henrique Hessel [UNESP] ; Terashima de Pinho, Marcus Vinicius [UNESP] ; Pena Ferreira, Marcelo Jose ; Romoff, Paulete ; Matioli, Fabio Filippi [UNESP] ; Magro, Angelo Jose [UNESP] ; Mattos Fontes, Marcos Roberto de [UNESP] ; Toyama, Marcos Hikari [UNESP]
Date: 2014
Persistent ID: http://hdl.handle.net/11449/113105
Origin: Oasisbr
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundo Mackenzie de Pesquisa
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Instituto Nacional para Pesquisa em Toxinas (INCT-Tox)
This paper shows the results of quercitrin effects on the structure and biological activity of secretory phospholipase (sPLA(2)) from Crotalus durissus terrificus, which is the main toxin involved in the pharmacological effects of this snake venom. According to our mass spectrometry and circular dichroism results, quercetin was able to promote a chemical modification of some amino acid residues and modify the secondary structure of C. d. terrificus sPLA(2). Moreover, molecular docking studies showed that quercitrin can establish chemical interactions with some of the crucial amino acid residues involved in the enzymatic activity of the sPLA(2), indicating that this flavonoid could also physically impair substrate molecule access to the catalytic site of the toxin. Additionally, in vitro and in vivo assays showed that the quercitrin strongly diminished the catalytic activity of the protein, altered its Vmax and Km values, and presented a more potent inhibition of essential pharmacological activities in the C. d. terrificus sPLA(2), such as its myotoxicity and edematogenic effect, in comparison to quercetin. Thus, we concluded that the rhamnose group found in quercitrin is most likely essential to the antivenom activities of this flavonoid against C. d. terrificus sPLA(2).
Univ Presbiteriana Mackenzie, CCBS, BR-01302907 Sao Paulo, Brazil
UNESP, BIOMOLPEP, Lab Biol Mol & Peptideos, BR-11330900 Sao Vicente, SP, Brazil
Univ Estadual Campinas, Fac Ciencias Med, Programa Posgrad Farmacol, BR-13083970 Campinas, SP, Brazil
Univ Presbiteriana Mackenzie, Escola Engn, BR-01302907 Sao Paulo, Brazil
UNESP, Inst Biociencias, Dept Fis & Biofis, BR-18618970 Botucatu, SP, Brazil
UNESP, BIOMOLPEP, Lab Biol Mol & Peptideos, BR-11330900 Sao Vicente, SP, Brazil
UNESP, Inst Biociencias, Dept Fis & Biofis, BR-18618970 Botucatu, SP, Brazil
FAPESP: 11/06704-4
FAPESP: 12/06502-5
FAPESP: 13/12077-8
