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Oncotarget. 2016 Jul 12;7(28):43088-43094. doi: 10.18632/oncotarget.9292.

Importance of the residue 190 on bactericidal activity of the bactericidal/permeability-increasing protein 5.

Author information

1
Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
2
Department of Cell Biology and Genetics, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen, China.

Abstract

The bactericidal/permeability-increasing protein (BPI) with bactericidal and endotoxin-neutralizing activity is of considerable interest in clinical applications. However, the crucial residues responsible for the bactericidal activity of BPI remain elusive. In previous study, we identified the mutation of mBPI5 associated with the male infertility of mice. Here, the effects of Asp190Ala mutation on the antibacterial activity of mBPI5 have been determined. Substitution of Asp190 by alanine caused significant improvement in cytotoxic effect toward both E.coli J5 and P.aeruginosa. Liposome co-sedimentation assay showed that the ratio of Asp190Ala mutant binding to lipids increased by 8 folds. These results were well consistent with known fact that antibacterial activity of BPI is attributed to its high affinity for lipid moiety of lipopolysaccharides (LPS). The constructed structure of mBPI5 revealed that Asp190 was located close to 6 positively charged residues on the surface of N-terminal domain. When replacing Asp190 with alanine, salt linkages with Arg188 were broken, making the side chain of Arg188 be free to move and form tighter contacts with negatively charged LPS. These findings suggest that residue 190 combined with surrounding positively charged residues largely contribute to bactericidal and endotoxin-neutralizing activities of mBPI5.

KEYWORDS:

BPI; charged residue; mutant; structural model

PMID:
27177329
PMCID:
PMC5190010
DOI:
10.18632/oncotarget.9292
[Indexed for MEDLINE]
Free PMC Article

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