Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR7272, Nice, 06108, France.
Université de Paris, INSERM, Biologie Intégrée du Globule Rouge, UMR_S1134, 75015, Paris, France.
Chembiochem. 2022 Feb 4;23(3):e202100553. doi: 10.1002/cbic.202100553. Epub 2021 Dec 16.
Flavonoids are secondary metabolites ubiquitously found in plants. Their antioxidant properties make them highly interesting natural compounds for use in pharmacology. Therefore, unravelling the mechanisms of flavonoid biosynthesis is an important challenge. Among all the enzymes involved in this biosynthetic pathway, dihydroflavonol-4-reductase (DFR) plays a key role in the production of anthocyanins and proanthocyanidins. Here, we provide new information on the mechanism of action of this enzyme by using QM/MM-MD simulations applied to both dihydroquercetin (DHQ) and dihydrokaempferol (DHK) substrates. The consideration of these very similar compounds shed light on the major role played by the enzyme on the stabilization of the transition state but also on the activation of the substrate before the reaction through near-attack conformer effects.
类黄酮是植物中普遍存在的次生代谢物。它们的抗氧化特性使它们成为药理学中非常有趣的天然化合物。因此，揭示类黄酮生物合成的机制是一个重要的挑战。在这个生物合成途径中涉及的所有酶中，二氢黄酮醇-4-还原酶（DFR）在花色苷和原花青素的生成中起着关键作用。在这里，我们通过应用 QM/MM-MD 模拟对二氢根皮素（DHQ）和二氢山柰酚（DHK）两种底物进行了酶作用机制的新信息。考虑到这些非常相似的化合物，阐明了该酶在稳定过渡态方面的主要作用，同时还通过近攻击构象效应，在反应之前对底物进行了激活。
