Set8和Suv4-h20是组蛋白H4上第20位赖氨酸（K）特异性的单和二、三甲基转移酶。Set8参与细胞周期调控，及由泛素化降解。研究证明Set8与前列腺癌和乳腺癌有关，而甲基转移酶抑制剂可以调节诱导性多功能干细胞（iPS）的细胞生产和重组，使得Set8成为一个非常有价值的药物靶标。有关酶活反应中间体及Set8和Suv4-h20的结构信息对于设计特异性的抑制剂是迫切需要的。最近，核磁共振（ NMR）波谱的巨大发展使人们可以观测出现频率低、能级高的蛋白质溶液构象，而这些存在的构象对于快速、高效的蛋白质折叠和酶催化的实现是必需的。虽然有关Set8和Suv4-h20功能的研究结果不断涌现，甲基转移酶这一类家族的催化的分子机制仍不清楚。本研究将利用NMR方法计来阐述它们的动力学特性、结构中间体及其催化作用机制。研究的结果将加深酶催化和蛋白质分子折叠机制的了解，推动癌症治疗和干细胞研究的发展。

Set8 and Suv4-h20 are histone H4 Lysine-20-specific mono-methyltransferase and di-, tri-methyltransferase respectively. Set8 regulates the cell cycle and is degraded through ubiquitination. Set8 correlates with prostate and breast cancers, and methyltransferase inhibitors can chemically modulate iPS cell production and reprogramming, making Set8 a valuable drug target. Knowledge of the unique structure-intermediates and structures of Set8 and Suv4-h20 is required to design their specific inhibitors. Recent monumental developments in nuclear magnetic resonance (NMR) spectroscopy have made it possible to study less populated high-energy protein conformations. The pre-existence of high-energy conformations is required for fast and efficient protein folding and enzyme catalysis. While new functions of Set8 and Suv4-20 are continuously emerging, the molecular mechanism of catalysis for this large class of enzymes remains unclear. In the proposed study, we plan to delineate the dynamics, kinetics, structure-intermediates and catalysis of these enzymes using NMR methods. The results of this study will deepen our understanding of the molecular mechanisms of enzyme catalysis and protein folding, and may lead to cancer treatments and stem cell developments.