Inhibitory Effect of Bovine Lactoferrin on Catechol-O-Methyltransferase
AbstractLactoferrin (LF) is a well-known multifunctional protein. In this study, we report the inhibitory potency of bovine LF (bLF) on catechol-O-methyltransferase (COMT), which catalyzes methylation of catechol substrates. We found that bLF binds to and inhibits COMT using its N-terminal region. An N-terminal peptide fragment obtained from bLF by trypsin digestion showed a higher inhibitory activity than intact bLF. A synthetic fragment of the bLF N-terminal residues 6–50, with two pairs of disulfide bonds, also showed higher inhibitory activity than intact bLF. Enzyme kinetic studies proved that bLF did not compete with S-adenosylmethionine (the methyl donor substrate) as well as methyl acceptor substrates such as dihydroxybenzoic acid, (−)-epicatechin, norepinephrine, or l-3,4-dihydroxyphenylalanine. The inhibitory potency of bLF decreased against a COMT preparation pretreated with dithiothreitol, suggesting that the oxidation status of COMT is relevant to interaction with bLF. We further confirmed that COMT activity in the cell extracts form Caco-2 and HepG2 cells was inhibited by bLF and by the synthesized fragment. Enzyme kinetic study indicated that bLF functions as a non-competitive inhibitor by binding to an allosteric surface of COMT. View Full-Text
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Ikeda, M.; Iijima, H.; Shinoda, I.; Iwamoto, H.; Takeda, Y. Inhibitory Effect of Bovine Lactoferrin on Catechol-O-Methyltransferase. Molecules 2017, 22, 1373.
Ikeda M, Iijima H, Shinoda I, Iwamoto H, Takeda Y. Inhibitory Effect of Bovine Lactoferrin on Catechol-O-Methyltransferase. Molecules. 2017; 22(8):1373.Chicago/Turabian Style
Ikeda, Masayuki; Iijima, Hiroshi; Shinoda, Ichizo; Iwamoto, Hiroshi; Takeda, Yasuhiro. 2017. "Inhibitory Effect of Bovine Lactoferrin on Catechol-O-Methyltransferase." Molecules 22, no. 8: 1373.
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