Dipartimento di Chimica, Università della Calabria, I-87036 Rende, CS, Italy.
J Agric Food Chem. 2010 Oct 13;58(19):10768-73. doi: 10.1021/jf102576j.
Density functional theory was applied to study the binding mode of new flavonoids as possible inhibitors of the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), an enzyme that catalyzes the four-electron reduction of HMGCoA to mevalonate, the committed step in the biosynthesis of sterols. The investigated flavonoid conjugates brutieridin and melitidin were recently quantified in the bergamot fruit extracts and identified to be structural analogues of statins, lipids concentration lowering drugs that inhibit HMGR. Computations allowed us to perform a detailed analysis of the geometrical and electronic features affecting the binding of these compounds, as well as that of the excellent simvastatin drug, to the active site of the enzyme and to give better insight into the inhibition process.
密度泛函理论被应用于研究新黄酮类化合物作为 3-羟基-3-甲基戊二酰辅酶 A 还原酶（HMGR）抑制剂的结合模式，HMGR 是一种酶，催化 HMGCoA 的四电子还原为甲羟戊酸，这是固醇生物合成中的关键步骤。最近在佛手柑果实提取物中定量了研究的黄酮类化合物布替里定和米替定，并被鉴定为他汀类药物的结构类似物，他汀类药物是降低脂质浓度的抑制 HMGR 的药物。计算允许我们对这些化合物以及优秀的辛伐他汀药物与酶的活性位点结合的几何和电子特性进行详细分析，并更好地了解抑制过程。
