Reversible and competitive inhibition of enteropeptidase by 1-trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64)

Masashi Matsushima, Naohisa Yahagi, Masao Ichinose, Kazumasa Miki, Masao Omata, Tsunehiko Higuchi, Hideshi Inoue, Takayuki Takahashi, Kenji Takahashi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

l-trans-Epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64), an well known cysteine proteinase inhibitor, which specifically inhibits cysteine proteinases by irreversibly modifying the free sulfhydryl group of the active site cysteine residue with its epoxide group, was shown to strongly inhibit the serine proteinase enteropeptidase, the key enzyme in the intestinal protein digestion cascade, in a reversible and competitive manner with a Ki value of 12 μM. The derivative of E-64, in which the epoxide group was reacted with 2-mercaptoethanol, also inhibited the enzyme, whereas 1-trans-epoxysuccinyl-L-leucylamido-3-methylbutane (E-64c), which lacks the guanidinium group, had no inhibitory effect on the enzyme, indicating that the guanidinium group is essential for the inhibition of enteropeptidase.

Original languageEnglish
Pages (from-to)207-210
Number of pages4
JournalBiomedical Research
Volume22
Issue number4
Publication statusPublished - 2001
Externally publishedYes

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Enteropeptidase
Epoxy Compounds
Guanidine
Enzymes
Cysteine Proteinase Inhibitors
Cysteine Proteases
Mercaptoethanol
Serine Proteases
Proteolysis
Cysteine
Catalytic Domain
Derivatives
E 64
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Matsushima, M., Yahagi, N., Ichinose, M., Miki, K., Omata, M., Higuchi, T., ... Takahashi, K. (2001). Reversible and competitive inhibition of enteropeptidase by 1-trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64). Biomedical Research, 22(4), 207-210.

Reversible and competitive inhibition of enteropeptidase by 1-trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64). / Matsushima, Masashi; Yahagi, Naohisa; Ichinose, Masao; Miki, Kazumasa; Omata, Masao; Higuchi, Tsunehiko; Inoue, Hideshi; Takahashi, Takayuki; Takahashi, Kenji.

In: Biomedical Research, Vol. 22, No. 4, 2001, p. 207-210.

Research output: Contribution to journalArticle

Matsushima, M, Yahagi, N, Ichinose, M, Miki, K, Omata, M, Higuchi, T, Inoue, H, Takahashi, T & Takahashi, K 2001, 'Reversible and competitive inhibition of enteropeptidase by 1-trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64)', Biomedical Research, vol. 22, no. 4, pp. 207-210.
Matsushima, Masashi ; Yahagi, Naohisa ; Ichinose, Masao ; Miki, Kazumasa ; Omata, Masao ; Higuchi, Tsunehiko ; Inoue, Hideshi ; Takahashi, Takayuki ; Takahashi, Kenji. / Reversible and competitive inhibition of enteropeptidase by 1-trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64). In: Biomedical Research. 2001 ; Vol. 22, No. 4. pp. 207-210.
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AU - Ichinose, Masao

AU - Miki, Kazumasa

AU - Omata, Masao

AU - Higuchi, Tsunehiko

AU - Inoue, Hideshi

AU - Takahashi, Takayuki

AU - Takahashi, Kenji

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AB - l-trans-Epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64), an well known cysteine proteinase inhibitor, which specifically inhibits cysteine proteinases by irreversibly modifying the free sulfhydryl group of the active site cysteine residue with its epoxide group, was shown to strongly inhibit the serine proteinase enteropeptidase, the key enzyme in the intestinal protein digestion cascade, in a reversible and competitive manner with a Ki value of 12 μM. The derivative of E-64, in which the epoxide group was reacted with 2-mercaptoethanol, also inhibited the enzyme, whereas 1-trans-epoxysuccinyl-L-leucylamido-3-methylbutane (E-64c), which lacks the guanidinium group, had no inhibitory effect on the enzyme, indicating that the guanidinium group is essential for the inhibition of enteropeptidase.

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