Active site mutants of human secreted Group IIA Phospholipase A(2) lacking hydrolytic activity retain their bactericidal effect

Autor(es)

Chioato, Lucimara ^[1] ; Aragao, Elisangela Aparecida ^[2] ; Ferreira, Tatiana Lopes ^[1] ; Ward, Richard J. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Biochem & Immunol, FMRP USP, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Quim, Fac Filosofia Ciencias & Letras Ribeirao Preto, FFCLRP USP, BR-14040901 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Biochimie; v. 94, n. 1, p. 132-136, JAN 2012.
• Citações Web of Science: 4

Resumo

The Human Secreted Group IIA Phospholipase A(2) (hsPIA2GIIA) presents potent bactericidal activity, and is considered to contribute to the acute-phase immune response. Hydrolysis of inner membrane phospholipids is suggested to underlie the bactericidal activity, and we have evaluated this proposal by comparing catalytic activity with bactericidal and liposome membrane damaging effects of the G30S, H48Q and D49K h5PLA2GIIA mutants. All mutants showed severely impaired hydrolytic activities against mixed DOPC:DOPG liposome membranes, however the bactericidal effect against Micrococcus luteus was less affected, with 50% killing at concentrations of 1, 3, 7 and 9 mu g/mL for the wild-type, D49K, H48Q and G30S mutants respectively. Furthermore, all proteins showed Ca2+-independent damaging activity against Liposome membranes demonstrating that in addition to the hydrolysis-dependent membrane damage, the hsPLA2GIIA presents a mechanism for permeabilization of phospholipid bilayers that is independent of catalytic activity, which may play a role in the bactericidal function of the protein (C) 2011 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 01/00279-8 - Papel dos resíduos positivamente carregados nas funções farmacológicas de PLA2s de serpentes e sinovial humana
• Beneficiário: Lucimara Chioato
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 02/12746-2 - Investigação de mudanças conformacionais de bothropstoxina I (PLA2-Lys49) do veneno de Bothrops jararacussu em associação com membranas artificiais
• Beneficiário: Tatiana Lopes Ferreira
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto