Fungal metabolite, epoxyquinol B, crosslinks proteins by epoxy-thiol conjugation

Hiroshi Kamiyama; Takeo Usui; Masakazu Uramoto; Hiroshi Takagi; Mitsuru Shoji; Yujiro Hayashi; Hideaki Kakeya; Hiroyuki Osada

doi:10.1038/ja.2008.117

Fungal metabolite, epoxyquinol B, crosslinks proteins by epoxy-thiol conjugation

Hiroshi Kamiyama, Takeo Usui, Masakazu Uramoto, Hiroshi Takagi, Mitsuru Shoji, Yujiro Hayashi, Hideaki Kakeya, Hiroyuki Osada

School of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Epoxyquinol B (EPQB) is a fungal metabolite, containing two α,/β-epoxy ketones. We previously showed that EPQB inhibited the signal transduction involved in angiogenesis through the binding to cysteine residues of receptor kinases. However, the inhibitory mechanism was undefined. In this report, we found that one EPQB molecule is covalently bound to two X-cysteine molecules through two epoxide residues on EPQB. Furthermore, EPQB crosslinked binding proteins through the cysteine residues. These results suggest that EPQB inhibits receptor kinases by crosslinking with other protein or by intramolecular crosslinking.

Original language	English
Pages (from-to)	94-97
Number of pages	4
Journal	Journal of Antibiotics
Volume	61
Issue number	2
DOIs	https://doi.org/10.1038/ja.2008.117
Publication status	Published - 2008 Feb

Keywords

Crosslink
Cysteine
Epoxide
Epoxyquinoid
Epoxyquinol B
Fungal metabolite

ASJC Scopus subject areas

Pharmacology
Drug Discovery

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10.1038/ja.2008.117

Cite this

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title = "Fungal metabolite, epoxyquinol B, crosslinks proteins by epoxy-thiol conjugation",

abstract = "Epoxyquinol B (EPQB) is a fungal metabolite, containing two α,/β-epoxy ketones. We previously showed that EPQB inhibited the signal transduction involved in angiogenesis through the binding to cysteine residues of receptor kinases. However, the inhibitory mechanism was undefined. In this report, we found that one EPQB molecule is covalently bound to two X-cysteine molecules through two epoxide residues on EPQB. Furthermore, EPQB crosslinked binding proteins through the cysteine residues. These results suggest that EPQB inhibits receptor kinases by crosslinking with other protein or by intramolecular crosslinking.",

keywords = "Crosslink, Cysteine, Epoxide, Epoxyquinoid, Epoxyquinol B, Fungal metabolite",

author = "Hiroshi Kamiyama and Takeo Usui and Masakazu Uramoto and Hiroshi Takagi and Mitsuru Shoji and Yujiro Hayashi and Hideaki Kakeya and Hiroyuki Osada",

note = "Funding Information: Acknowledgment This study was supported in part by Junior",

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doi = "10.1038/ja.2008.117",

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AU - Kamiyama, Hiroshi

AU - Usui, Takeo

AU - Uramoto, Masakazu

AU - Takagi, Hiroshi

AU - Shoji, Mitsuru

AU - Hayashi, Yujiro

AU - Kakeya, Hideaki

AU - Osada, Hiroyuki

N1 - Funding Information: Acknowledgment This study was supported in part by Junior

PY - 2008/2

Y1 - 2008/2

N2 - Epoxyquinol B (EPQB) is a fungal metabolite, containing two α,/β-epoxy ketones. We previously showed that EPQB inhibited the signal transduction involved in angiogenesis through the binding to cysteine residues of receptor kinases. However, the inhibitory mechanism was undefined. In this report, we found that one EPQB molecule is covalently bound to two X-cysteine molecules through two epoxide residues on EPQB. Furthermore, EPQB crosslinked binding proteins through the cysteine residues. These results suggest that EPQB inhibits receptor kinases by crosslinking with other protein or by intramolecular crosslinking.

AB - Epoxyquinol B (EPQB) is a fungal metabolite, containing two α,/β-epoxy ketones. We previously showed that EPQB inhibited the signal transduction involved in angiogenesis through the binding to cysteine residues of receptor kinases. However, the inhibitory mechanism was undefined. In this report, we found that one EPQB molecule is covalently bound to two X-cysteine molecules through two epoxide residues on EPQB. Furthermore, EPQB crosslinked binding proteins through the cysteine residues. These results suggest that EPQB inhibits receptor kinases by crosslinking with other protein or by intramolecular crosslinking.

KW - Crosslink

KW - Cysteine

KW - Epoxide

KW - Epoxyquinoid

KW - Epoxyquinol B

KW - Fungal metabolite

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Fungal metabolite, epoxyquinol B, crosslinks proteins by epoxy-thiol conjugation

Abstract

Keywords

ASJC Scopus subject areas

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