Zinkle Allen P, Morgan Ryan T, Nygaard Rie, Mancia Filippo
Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Radiation Oncology, Weill Cornell Medical College, New York, NY 10065, USA.
Structure. 2025 Apr 3;33(4):639-651. doi: 10.1016/j.str.2025.01.003. Epub 2025 Jan 29.
Glycosyltransferases (GTs) catalyze the addition of sugars to diverse substrates facilitating complex glycoconjugate biosynthesis across all domains of life. When embedded in or associated with the membrane, these enzymes often depend on polyisoprenyl-phosphate or -pyrophosphate (PP) lipid carriers, including undecaprenyl phosphate in bacteria and dolichol phosphate in eukaryotes, to transfer glycan moieties. GTs that bind PP substrates (PP-GTs) are functionally diverse but share some common structural features within their family or subfamily, particularly with respect to how they interact with their cognate PP ligands. Recent advances in single-particle cryo-electron microscopy (cryo-EM) have provided insight into the structures of PP-GTs and the modes by which they bind their PP ligands. Here, we explore the structural landscape of PP-GTs, focusing mainly on those for which there is molecular-level information on liganded states, and highlight how PP coordination modalities may be shared or differ among members of this diverse enzyme class.
糖基转移酶（GTs）催化糖类添加到各种底物上，促进了所有生命域中复杂糖缀合物的生物合成。当这些酶嵌入膜中或与膜相关联时，它们通常依赖多异戊二烯基磷酸酯或焦磷酸酯（PP）脂质载体，包括细菌中的十一异戊烯基磷酸酯和真核生物中的多萜醇磷酸酯，来转移聚糖部分。结合PP底物的GTs（PP-GTs）功能多样，但在其家族或亚家族中具有一些共同的结构特征，特别是在它们与同源PP配体相互作用的方式方面。单颗粒冷冻电子显微镜（cryo-EM）的最新进展为PP-GTs的结构及其结合PP配体的模式提供了深入了解。在这里，我们探讨PP-GTs的结构概况，主要关注那些有关于配体状态的分子水平信息的PP-GTs，并强调这种多样酶类成员之间PP配位方式可能如何共享或不同。
