MT3/QR2 melatonin binding site does not use melatonin as a substrate or a co‐substrate

Abstract

Quinone reductase 2 (QR2, E.C. 1.10.99.2) is implicated in cell reactive oxygen species production. The catalytic activity of this enzyme is inhibited by 1 microM of melatonin. QR2 was identified as the third melatonin binding site (MT3). It is of major importance to understand the exact roles of melatonin and QR2 in oxidative stress. A fascinating possibility that melatonin could serve as a co-substrate or substrate of QR2 was hypothesized recently. In the current investigation, nuclear magnetic resonance studies of the QR2 catalytic reaction were performed, the results led us to conclude that, whatever the conditions, melatonin is not cleaved off to form N1-acetyl-N2-formyl-5-methoxykynurenine by a catalytically active QR2, very strongly indicating that melatonin is neither a substrate nor a co-substrate of this enzyme. Further studies are needed in order to better understand the relationship between MT3/QR2, melatonin and redox status of the cells, in order to better explain the anti-oxidant activities of melatonin at pharmacological concentrations (>1 microM).

Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis

“…These effects could be related to the activation of melatonin membrane receptors by AFMK, because luzindole (antagonist of these receptors) reversed AFMK-induced stimulation of HSPs in PANC-1 cells [94]. The observation concerning the involvement of MT 1 /MT 2 receptor in the effect of AFMK is in agreement with previous reports, showing that AFMK is able to bind to the melatonin membrane receptor, but its affinity to this receptor is lower than that of melatonin [34,95,96,97,98,99]. …”

An insight into the scientific background and future perspectives for the potential uses of melatonin

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