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Biochimie. 2012 Jun;94(6):1437-40. doi: 10.1016/j.biochi.2012.03.020. Epub 2012 Apr 2.

The bactericidal effect of human secreted group IID phospholipase A2 results from both hydrolytic and non-hydrolytic activities.

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  • 1Department of Biochemistry and Immunology, FMRP-USP, Universidade de São Paulo, Brazil.

Abstract

The Human Secreted Group IID Phospholipase A(2) (hsPLA2GIID) may be involved in the human acute immune response. Here we have demonstrated that the hsPLA2GIID presents bactericidal and Ca(2+)-independent liposome membrane-damaging activities and we have compared these effects with the catalytic activity of active-site mutants of the protein. All mutants showed reduced hydrolytic activity against DOPC:DOPG liposome membranes, however bactericidal effects against Escherichia coli and Micrococcus luteus were less affected, with the D49K mutant retaining 30% killing of the Gram-negative bacteria at a concentration of 10μg/mL despite the absence of catalytic activity. The H48Q mutant maintained Ca(2+)-independent membrane-damaging activity whereas the G30S and D49K mutants were approximately 50% of the wild-type protein, demonstrating that phospholipid bilayer permeabilization by the hsPLA2GIID is independent of catalytic activity. We suggest that this Ca(2+)-independent damaging activity may play a role in the bactericidal function of the protein.

Copyright © 2012 Elsevier Masson SAS. All rights reserved.

PMID:
22490726
[PubMed - indexed for MEDLINE]
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