School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China; Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center), Guangzhou, China.
School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China; Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center), Guangzhou, China.
Int J Biol Macromol. 2018 Oct 15;118(Pt A):588-598. doi: 10.1016/j.ijbiomac.2018.06.045. Epub 2018 Jun 15.
In this work, the hydroxyl-related differences of binding properties and inhibitory activities of dietary flavonoids, namely chrysin, baicalein and apigenin against purine nucleoside phosphorylase (PNP) were investigated. It was found that the hydroxylation on position C4' of chrysin (→apigenin) mildly decreased the binding affinities for PNP, whereas on the position C6 of chrysin (→baicalein) significantly increased binding affinities. Comparatively, the hydroxylation on position C4' and C6 greatly improved their PNP inhibitory effects. The IC values of apigenin and baicalein were 6.09 × 10 M and 8.94 × 10 M, respectively, which is significantly lower than that of chrysin (2.13 × 10 M). Results from molecular modeling revealed that there are two binding sites, i.e. active site (major) and tryptophan site (minor) on PNP, and the binding of these flavonoids might induce a serious conformational destabilization of PNP as a result of altering the micro-environment and morphology by flavonoids.
在这项工作中，研究了膳食类黄酮（包括白杨黄素、黄芩素和芹菜素）中与羟基相关的结合特性和抑制活性差异对嘌呤核苷磷酸化酶（PNP）的影响。结果发现，白杨黄素 C4'位的羟化（→芹菜素）轻微降低了与 PNP 的结合亲和力，而白杨黄素 C6 位的羟化（→黄芩素）显著增加了与 PNP 的结合亲和力。相比之下，C4'和 C6 位的羟化大大提高了它们对 PNP 的抑制作用。芹菜素和黄芩素的 IC 值分别为 6.09×10-6 M 和 8.94×10-6 M，明显低于白杨黄素（2.13×10-6 M）。分子建模结果表明，PNP 上有两个结合位点，即活性位点（主要）和色氨酸位点（次要），这些黄酮类化合物的结合可能导致 PNP 严重的构象不稳定，这是由于黄酮类化合物改变了微环境和形态。
