Mistry Ravina, Byrne Dominic P, Starns David, Barsukov Igor L, Yates Edwin A, Fernig David G
Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7ZB, U.K.
Essays Biochem. 2024 Dec 4;68(4):431-447. doi: 10.1042/EBC20230094.
The vast structural diversity of sulfated polysaccharides demands an equally diverse array of enzymes known as polysaccharide sulfotransferases (PSTs). PSTs are present across all kingdoms of life, including algae, fungi and archaea, and their sulfation pathways are relatively unexplored. Sulfated polysaccharides possess anti-inflammatory, anticoagulant and anti-cancer properties and have great therapeutic potential. Current identification of PSTs using Pfam has been predominantly focused on the identification of glycosaminoglycan (GAG) sulfotransferases because of their pivotal roles in cell communication, extracellular matrix formation and coagulation. As a result, our knowledge of non-GAG PSTs structure and function remains limited. The major sulfotransferase families, Sulfotransfer_1 and Sulfotransfer_2, display broad homology and should enable the capture of a wide assortment of sulfotransferases but are limited in non-GAG PST sequence annotation. In addition, sequence annotation is further restricted by the paucity of biochemical analyses of PSTs. There are now high-throughput and robust assays for sulfotransferases such as colorimetric PAPS (3'-phosphoadenosine 5'-phosphosulfate) coupled assays, Europium-based fluorescent probes for ratiometric PAP (3'-phosphoadenosine-5'-phosphate) detection, and NMR methods for activity and product analysis. These techniques provide real-time and direct measurements to enhance the functional annotation and subsequent analysis of sulfated polysaccharides across the tree of life to improve putative PST identification and characterisation of function. Improved annotation and biochemical analysis of PST sequences will enhance the utility of PSTs across biomedical and biotechnological sectors.
硫酸化多糖巨大的结构多样性需要同样多样的一系列酶，即多糖硫酸转移酶（PSTs）。PSTs存在于包括藻类、真菌和古菌在内的所有生命王国中，其硫酸化途径相对未被探索。硫酸化多糖具有抗炎、抗凝和抗癌特性，具有巨大的治疗潜力。目前使用Pfam对PSTs的鉴定主要集中在糖胺聚糖（GAG）硫酸转移酶的鉴定上，因为它们在细胞通讯、细胞外基质形成和凝血中起关键作用。因此，我们对非GAG PSTs结构和功能的了解仍然有限。主要的硫酸转移酶家族Sulfotransfer_1和Sulfotransfer_2显示出广泛的同源性，应该能够捕获各种各样的硫酸转移酶，但在非GAG PST序列注释方面存在局限性。此外，PSTs生化分析的匮乏进一步限制了序列注释。现在有用于硫酸转移酶的高通量和可靠检测方法，如比色PAPS（3'-磷酸腺苷5'-磷酸硫酸）偶联检测、用于比例PAP（3'-磷酸腺苷-5'-磷酸）检测的基于铕的荧光探针以及用于活性和产物分析的NMR方法。这些技术提供实时和直接测量，以加强对生命之树上硫酸化多糖的功能注释和后续分析，从而改进推定的PST鉴定和功能表征。改进PST序列的注释和生化分析将提高PSTs在生物医学和生物技术领域的效用。
