Regioselective sulfation and glucuronidation of phenolics: insights into the structural basis.
Regioselective sulfation and glucuronidation of phenolics: insights into the structural basis.
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DOI：
10.2174/138920011797470100
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发表时间：
2011-11
影响因子：
2.3
通讯作者：
Hu M
中科院分区：
文献类型：
--
作者：
Wu B;Basu S;Meng S;Wang X;Hu M
分别由磺基转移酶 (SULT) 和 UDP-葡萄糖醛酸基转移酶 (UGT) 介导的 II 相代谢硫酸化和葡萄糖醛酸化是许多内生素和外生素的重要代谢途径。了解 SULT/UGT 底物特异性（包括区域选择性（即位置偏好））对于预测硫酸化/葡萄糖醛酸化对体内药物和代谢物处置的贡献非常重要。本综述总结了具有多个羟基 (OH) 基团作为潜在缀合位点的酚类化合物的区域选择性硫酸化和葡萄糖醛酸化。强调了几种 SULT 和 UGT 同工型对黄酮类化合物（一大类天然多酚）的严格区域选择性模式。为了寻求分子水平的解释，采用了酶结构（即 SULT 晶体结构和基于同源性的 UGT 结构模型）与分子对接相结合。特别是，讨论了 SULT1A3 和 UGT1A1 区域选择性代谢黄酮类化合物的结构基础。结论是这些 II 相酶的区域选择性性质是由结合袋的大小和形状决定的。虽然酶的分子结构可用于解释有关结合特性的区域选择性代谢，但预测不同位置的转换仍然是一项特别困难的任务。
The phase II metabolism sulfation and glucuronidation, mediated by sulfotransferases (SULTs) and UDP-glucuronosyltransferases (UGTs) respectively, are significant metabolic pathways for numerous endo- and xenobiotics. Understanding of SULT/UGT substrate specificity (including regioselectivity (i.e., position preference)) is of great importance in predicting contribution of sulfation/glucuronidation to drug and metabolite disposition in vivo. This review summarizes regioselective sulfation and glucuronidation of phenolic compounds with multiple hydroxyl (OH) groups as the potential conjugation sites. The strict regioselective patterns were highlighted for several SULT and UGT isoforms towards flavonoids, a large class of natural polyphenols. To seek for a molecular-level explanation, the enzyme structures (i.e., SULT crystal structures and homology-based UGT structure models) combined with molecular docking was employed. In particular, the structural bases for regioselective metabolism of flavonoids by SULT1A3 and UGT1A1 were discussed. It was concluded that the regioselective nature of these phase II enzymes was determined by the size and shape of binding pocket. While the molecular structures of the enzymes can be used to explain regioselective metabolism regarding the binding property, predicting the turnover at different positions remains a particularly difficult task.
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DOI：
10.1016/j.bbrc.2005.07.091
发表时间：
2005-09-23
影响因子：
3.1
作者：
Lu, JH;Li, HT;Chang, WR
通讯作者：
Chang, WR
影响因子：
4.5
作者：
Liu, Wei;Tang, Lan;Liu, Zhongqiu
通讯作者：
Liu, Zhongqiu
影响因子：
2.1
作者：
Fujiwara, Ryoichi;Nakajima, Miki;Yokoi, Tsuyoshi
通讯作者：
Yokoi, Tsuyoshi
影响因子：
1.8
作者：
Locuson, C. W.;Tracy, T. S.
通讯作者：
Tracy, T. S.
多变量外显子的适应性演变和药物代谢酶的结构多样性。
影响因子：
3.4
作者：
Li, Can;Wu, Qiang
通讯作者：
Wu, Qiang