STRUCTURE DETERMINATION OF HUMAN O-GLCNAC TRANSFERASE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 O-GlcNAc转移酶(OGT)是一种人类糖基转移酶，负责细胞质和核蛋白的所有O-GlcN酰化。O-GlcN酰化是蛋白质在丝氨酸和苏氨酸残基上的动态、可逆、翻译后修饰，调节蛋白质的活性、定位、信号和降解。这种修饰与许多疾病有关，包括糖尿病、癌症和阿尔茨海默氏症。更好地了解OGT，将有助于更好地理解这种修饰在细胞功能和人类疾病中的作用。我们正在努力解决OGT的晶体结构问题，以便更好地了解OGT的作用机制和细胞功能，并开发有效的、细胞通透性的OGT抑制剂，研究其在细胞培养和动物模型中的作用，这将有助于我们评估OGT作为治疗靶点的作用。我们已经获得了OGT的衍射晶，并接近于结构的求解，额外的数据将极大地提高我们解算结构到高分辨率的能力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. O-GlcNAc transferase (OGT) is a human glycosyltransferase that is responsible for all the O-GlcNAcylation of cytoplasmic and nuclear proteins. O-GlcNAcylation is a dynamic, reversible, post-translational modification of proteins on serine and threonine residues that modulates protein activity, localization, signaling, and degradation. This modification has been implicated in numerous diseases, including Diabetes, cancer, and Alzheimer's. Better knowledge of OGT and would lead to an improved understanding of the role of this modification in cellular functions and human diseases. We are trying to solve the crystal structure of OGT in order to gain a better understanding of its mechanism and cellular function, and also to develop potent, cell-permeable inhibitors of OGT to study its role in cell culture and animal models, which will help us evaluate OGT's utility as a therapeutic target. We have obtained diffracting crystals of OGT and are close to solving the structure and additional data would greatly enhance our ability to solve the structure to high resolution.