MT3/QR2 melatonin binding site does not use melatonin as a substrate or a co-substrate
MT3/QR2 melatonin binding site does not use melatonin as a substrate or a co-substrate
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DOI：
10.1111/j.1600-079x.2008.00631.x
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发表时间：
2008-11-01
影响因子：
10.3
通讯作者：
Ferry, Gilles
中科院分区：
文献类型：
--
作者：
Boutin, Jean A.;Marcheteau, Estelle;Ferry, Gilles
醌还原酶2 （QR2， E.C. 1.10.99.2）参与细胞活性氧的产生。1 μ M褪黑素可抑制该酶的催化活性。QR2被确定为第三个褪黑激素结合位点（MT3）。了解褪黑激素和QR2在氧化应激中的确切作用具有重要意义。最近提出了一种有趣的可能性，即褪黑激素可以作为QR2的共底物或底物。在目前的研究中，对QR2催化反应进行了核磁共振研究，结果使我们得出结论，无论在什么条件下，褪黑激素都不会被具有催化活性的QR2裂解成n1 -乙酰- n2 -甲酰基-5-甲氧基犬尿氨酸，这非常强烈地表明褪黑激素既不是该酶的底物，也不是该酶的共底物。为了更好地理解MT3/QR2、褪黑素与细胞氧化还原状态之间的关系，更好地解释褪黑素在药理学浓度（> 1 μ M）下的抗氧化活性，还需要进一步的研究。
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 mu M 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 mu M).