STRUCTURE DETERMINATION OF HUMAN O-GLCNAC TRANSFERASE

人 O-GLCNAC 转移酶的结构测定

• 批准号: 8170598
• 负责人: Piotr Sliz
• 金额: $ 1.19万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170598
• 关键词: Alzheimer' s Disease; Animal Model; Cell Culture Techniques; Cell physiology; Cells; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Data; Diabetes Mellitus; Disease; Funding; Grant; Human; Institution; Knowledge; Lead; Malignant Neoplasms; Modification; Nuclear Protein; Nuclear Proteins; O-GlcNAc transferase; Post-Translational Protein Processing; Proteins; Research; Research Personnel; Resolution; Resources; Role; Serine; Signal Transduction; Source; Structure; Threonine; UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; United States National Institutes of Health; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 O-GlcNAc转移酶（OGT）是一种人糖基转移酶，负责细胞质和核蛋白的所有O-GlcNAc酰化。O-GlcNAc酰化是丝氨酸和苏氨酸残基上的蛋白质的动态、可逆、翻译后修饰，其调节蛋白质活性、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。更好地了解OGT，将导致更好地理解这种修饰在细胞功能和人类疾病中的作用。我们正试图解决OGT的晶体结构，以便更好地了解其机制和细胞功能，并开发有效的，细胞可渗透的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。我们已经获得了衍射晶体的OGT和接近解决的结构和额外的数据将大大提高我们的能力，解决结构的高分辨率。