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The potent inhibitory activity of histone H1.2 C‐terminal fragments on furin
Author(s) -
Han Jinbo,
Zhang Ling,
Shao Xiaoxia,
Shi Jiahao,
Chi Chengwu
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05451.x
Subject(s) - furin , proprotein convertase , biochemistry , microbiology and biotechnology , chemistry , biology , peptide , enzyme , lipoprotein , ldl receptor , cholesterol
Many physiologically important proproteins, pathogenic bacterial exotoxins and viral envelope glycoproteins are activated by the proprotein convertase furin, which makes furin inhibitor a hot target for basic research and drug design. Although synthetic and bioengineered inhibitors of furin have been well characterized, its endogenous inhibitor has not been directly purified from mammalian tissues to date. In this study, three inhibitors were purified from the porcine liver by using a combination of chromatographic techniques, and identified to be the C‐terminal truncated fragments with different sizes of histone H1.2. The gene of porcine histone H1.2 was cloned and sequenced, further confirming the determined sequences. These three C‐terminal fragments inhibited furin with K i values around 2 × 10 −7 m while the full‐length histone H1.2 inhibited it with a lesser activity, suggesting that the inhibitory activity relies on the C‐terminal lysine‐rich domain. Though the inhibition was temporary, these inhibitors were specific, and the reactive site of one C‐terminal fragment was identified. A 36 amino acid peptide around the reactive site was synthesized, which could still inhibit furin with a K i of 5.2 × 10 −7 m .