Note

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

Received: January 7, 2008 / Accepted: February 8, 2008
© Japan Antibiotics Research Association

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 L-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 epoxyquinol B, crosslink, epoxide, cysteine, epoxyquinoid, fungal metabolite


H. Osada (Corresponding author), H. Kamiyama, T. Usui, M. Uramoto, H. Takagi, H. Kakeya: Antibiotics Laboratory, RIKEN Discovery Research Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan, E-mail: hisyo@riken.jp
H. Kamiyama, H. Osada: Graduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan
T. Usui: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan
M. Shoji, Y. Hayashi: Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagura-zaka, Shinjuku-ku, Tokyo 162-8601, Japan
Present address: Department of Chemistry, Graduate School of Science, Tohoku University, 6-3 Aramaki-Aza, Aoba, Sendai 980-8578, Japan
†† Present address: Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi, Sakyo-ku, Kyoto 606-8501, Japan