Next Article in Journal
Synthesis and Antimicrobial Studies of New Antibacterial Azo-Compounds Active against Staphylococcus aureus and Listeria monocytogenes
Previous Article in Journal
Impact of Xanthylium Derivatives on the Color of White Wine
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Molecules 2017, 22(8), 1373; doi:10.3390/molecules22081373

Inhibitory Effect of Bovine Lactoferrin on Catechol-O-Methyltransferase

1
Wellness & Nutrition Science Institute, R&D Division, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa 252-8583, Japan
2
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)
View Full-Text   |   Download PDF [2068 KB, uploaded 19 August 2017]   |  

Abstract

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
Figures

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).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Ikeda, M.; Iijima, H.; Shinoda, I.; Iwamoto, H.; Takeda, Y. Inhibitory Effect of Bovine Lactoferrin on Catechol-O-Methyltransferase. Molecules 2017, 22, 1373.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top