https://english.cas.cn/newsroom/research_news/life/202406/t20240621_665495.shtml
https://www.nature.com/articles/s41467-024-49516-2
A research team led by CHENG Xi and WEN Liuqing from the Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences, WANG Dingyan from the Lingang Laboratory, along with the collaborators, introduced a new carbohydrate-binding site predictor DeepGlycanSite. This predictor outperforms previous state-of-the-art methods and effectively predicts binding sites for diverse carbohydrates. Incorporating geometric and evolutionary features of proteins into a deep equivariant graph neural network with transformer architecture, DeepGlycanSite is capable of accurately predicting carbohydrate-binding sites on a given protein structure.
DeepGlycanSite can predict the specific binding site for a query carbohydrate.
The researchers built a network model, DeepGlycanSite+Ligand, to process protein structure and two-dimensional chemical structure of the query carbohydrate, with extra modules for dealing with ligand parts. DeepGlycanSite+Ligand could distinguish the specific binding site of the query carbohydrate belonging to various classes, while previous state-of-the-art methods showed inefficacy in distinguishing mono-, di-, or oligosaccharide-binding sites.
To set an example of its application, researchers used DeepGlycanSite+Ligand to identify the specific carbohydrate-binding site on a functionally important G-protein coupled receptor, P2Y purinoceptor 14 (P2Y14). P2Y14 regulates immune responses and associates with asthma, kidney injury and lung inflammation. In the calcium mobilization assay, guanosine 5’-diphosphatefucose (GDP-Fuc) is found to activate human P2Y14. As an essential sugar nucleotide in mammals, GDP-Fuc is critically involved in tumor growth and metastasis across various cancers. The GDP-Fuc-induced activation of P2Y14 has not been reported before. Hence, how GDP-Fuc acts on this receptor is unknown. The researchers also used DeepGlycanSite to identify that G80, D81 and N90 form the guanosine-5’-diphosphate-sugar-recognition site of P2Y14, and the findings were validated in mutagenesis studies.