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Molecules 2017, 22(8), 1373;

Inhibitory Effect of Bovine Lactoferrin on Catechol-O-Methyltransferase

Wellness & Nutrition Science Institute, R&D Division, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa 252-8583, Japan
School of Pharmacy, Nihon University, Funabashi, Chiba 274-8555, Japan
Author to whom correspondence should be addressed.
Received: 19 July 2017 / Revised: 8 August 2017 / Accepted: 16 August 2017 / Published: 19 August 2017
(This article belongs to the Section Medicinal Chemistry)
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Lactoferrin (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
Keywords: enzyme inhibitor; multifunctional protein; lactoferrin; catechol-O-methyltransferase enzyme inhibitor; multifunctional protein; lactoferrin; catechol-O-methyltransferase

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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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.

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