Abstract
Aim:
To examine the antimicrobial spectrum and functional structure of high mobility group nucleosomal binding domain 2 (HMGN2).
Methods:
OMIGA protein structure software was used to analyze the two-dimensional structure of HMGN2. Synthetic short peptides were generated for studying the relationship between function and structure. Prokaryotic expression vectors were constructed for the holo-HMGN2 and its helical domain. Their E coli-based products were also prepared for antimicrobial testing. The antimicrobial assay included minimal effective concentration, minimal inhibitory concentration, and minimal bactericidal concentration.
Results:
OMIGA protein structure software analysis revealed a transmembrane α-helical structure (the putative antimicrobial domain) located from position 18 to 48 of the HMGN2 protein sequence. The antimicrobial assay showed that the MIC of the recombinant holo-HMGN2 against E coli ML-35p (an ampicillin-resistance strain), Pseudomonas aeruginosa ATCC 27853 and Candida albicans ATCC 10231 were 12.5, 25, and 100 mg/L, respectively. Against the same microorganisms, the MIC of the synthetic HMGN2 α-helical domain were 12.5, 25, and 100 mg/L, respectively, that is, the same as with the recombinant form of HMGN2. In contrast, recombinant holo-HMGN2 was inactive against Staphylococcus aureus ATCC 25923. The synthetic N-terminal and C-terminal fragments of HMGN2 had no antimicrobial activity against E coli ML-35p, P aeruginosa ATCC 27853 or C albicans ATCC 10231.
Conclusion:
HMGN2 showed potent antimicrobial activity against E coli ML-35p, P aeruginosa ATCC 27853 and, to some extent, against C albicans ATCC 10231, but was inactive against S aureus ATCC 25923 in these assay systems. Its α-helical structure may be essential for the antimicrobial activity of HMGN2.
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Project supported by the National Natural Science Foundation of China (No 30300127 to YF) and China Medical Board of New York Inc (No 98–681 to BW).
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Feng, Y., Huang, N., Wu, Q. et al. α-Helical domain is essential for antimicrobial activity of high mobility group nucleosomal binding domain 2 (HMGN2). Acta Pharmacol Sin 26, 1087–1092 (2005). https://doi.org/10.1111/j.1745-7254.2005.00132.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00132.x