STRUCTURE DETERMINATION OF HUMAN O-GLCNAC TRANSFERASE

人 O-GLCNAC 转移酶的结构测定

• 批准号: 8363336
• 负责人: Piotr Sliz
• 金额: $ 1.61万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363336
• 关键词: Alzheimer' s Disease; Animal Model; Cell Culture Techniques; Cell physiology; Cells; Crystallography; Cytoplasmic Protein; Data; Diabetes Mellitus; Disease; Funding; Grant; Human; Knowledge; Lead; Light; Malignant Neoplasms; Modification; National Center for Research Resources; Nuclear Proteins; O-GlcNAc transferase; Post-Translational Protein Processing; Principal Investigator; Proteins; Research; Research Infrastructure; Resolution; Resources; Role; Serine; Signal Transduction; Source; Structure; Synchrotrons; Threonine; United States National Institutes of Health; cost; glycosyltransferase; human disease; improved; inhibitor/antagonist; therapeutic target

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 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-GlcNAc 酰化。 O-GlcNAcylation 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，可调节蛋白质活性、定位、信号传导和降解。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。对 OGT 的更好了解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。我们正在尝试解决OGT的晶体结构，以便更好地了解其机制和细胞功能，并开发强效的、细胞渗透性的OGT抑制剂，以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 作为治疗靶点的效用。我们已经获得了 OGT 的衍射晶体，并且接近求解其结构，额外的数据将大大增强我们求解高分辨率结构的能力。