Graduate School of Pharmaceutical Science, Osaka University, Suita, Osaka 565-0871, Japan.
National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan.
Acta Crystallogr D Struct Biol. 2022 Mar 1;78(Pt 3):379-389. doi: 10.1107/S2059798322000869. Epub 2022 Feb 21.
Capsaicinoids are phenolic compounds that have health benefits. However, the pungency and poor water solubility of these compounds limit their exploitation. Glycosylation is a powerful method to improve water solubility and reduce pungency while preserving bioactivity. PaGT3, a uridine diphosphate glycosyltransferase (UGT) from Phytolacca americana, is known for its ability to glycosylate capsaicinoids and other phenolic compounds. While structural information on several UGTs is available, structures of UGTs that can glycosylate a range of phenolic compounds are rare. To fill this gap, crystal structures of PaGT3 with a sugar-donor analogue (UDP-2-fluoroglucose) and the acceptors capsaicin and kaempferol were determined. PaGT3 adopts a GT-B-fold structure that is highly conserved among UGTs. However, the acceptor-binding pocket in PaGT3 is hydrophobic and large, and is surrounded by longer loops. The larger acceptor-binding pocket in PaGT3 allows the enzyme to bind a range of compounds, while the flexibility of the longer loops possibly plays a role in accommodating the acceptors in the binding pocket according to their shape and size. This structural information provides insights into the acceptor-binding mechanism in UGTs that bind multiple substrates.
辣椒素类化合物是具有健康益处的酚类化合物。然而，这些化合物的刺激性和较差的水溶性限制了它们的开发利用。糖基化是一种提高水溶性和降低刺激性同时保持生物活性的有效方法。来自美洲商陆的尿苷二磷酸糖基转移酶（UGT）PaGT3 因其能够糖基化辣椒素类化合物和其他酚类化合物而闻名。虽然有几种 UGT 的结构信息，但能够糖基化一系列酚类化合物的 UGT 结构却很少见。为了填补这一空白，确定了 PaGT3 与糖供体类似物（UDP-2-氟葡萄糖）和受体辣椒素和山柰酚的晶体结构。PaGT3 采用 GT-B 折叠结构，在 UGT 中高度保守。然而，PaGT3 的受体结合口袋是疏水的且较大，并被较长的环包围。PaGT3 较大的受体结合口袋允许该酶结合一系列化合物，而较长的环的灵活性可能在根据受体的形状和大小将其容纳在结合口袋中起作用。该结构信息提供了对结合多种底物的 UGT 中受体结合机制的深入了解。
