STRUCTURE DETERMINATION OF HUMAN O-GLCNAC TRANSFERASE

点击翻译按钮获取中文摘要

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.