癌症发病率与死亡率持续上升。癌症已成为我国死亡的主要原因。神经节苷脂GD3 及其下游产物GD2在癌症发生、发展中发挥重要作用。GD3合成酶（GD3 synthase，GD3s）是合成GD3的唯一关键酶，GD3s在肿瘤的侵袭和迁移中发挥重要的作用。目前GD3s的活性位点及催化机制还是不清楚，也没有它的抑制剂。我们构建了GD3s真核表达质粒和原核表达质粒并表达具有活性的GD3s蛋白，并利用该活性蛋白建立基于酶催化的高通量筛选模型。我们认为GD3s是个潜在的重要药物靶点，其抑制剂对治疗癌症具有重要意义。本研究将利用生物信息学，分子生物学和生物物理学的技术方法对GD3s的结构和功能展开研究，进一步确定GD3s为肿瘤潜在重要靶点；建立同源模型进行虚拟筛选结合基于酶催化的高通量筛选模型筛选GD3s抑制剂。GD3s的活性位点确立、催化机制的阐明及GD3s抑制剂的发现对癌症的发现和治疗具有重要意义。

Cancer incidence and mortality rates continue to rise. Cancer has become the main cause of death in China. Ganglioside GD3 and its downstream product GD2 play important roles in the occurrence and development of cancer. GD3 synthase (GD3s) is the only key enzyme in the synthesis of GD3, which plays an important role in tumor invasion and migration. So far, the active site and catalytic mechanism of GD3s are still unclear, and there are no GD3s inhibitors. We constructed GD3s eukaryotic expression plasmid and prokaryotic expression plasmid and expressed the active GD3s protein, and established a high throughput screening model based on enzyme catalysis. We propose that GD3s is an important drug target, and its inhibitors are of great significance in the treatment of cancer. In this study we will use multiple methods of bioinformatics, molecular biology and biophysics to study the structure and function of GD3s, to further determine that GD3s is a potential tumor target. Besides, we will establish virtual screening based on computation modeling, combined with high-throughput screening model based on enzyme catalysis, to screen GD3s inhibitors. The determination of the active site of GD3s, the elucidation of the catalytic mechanism and the discovery of GD3s inhibitors are of great significance to the diagnosis and treatment of cancer.