O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value.
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http://dx.doi.org/10.1038/nchembio.2358 | DOI Listing |
Biol Trace Elem Res
January 2025
Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, AvInstituto Politécnico Nacional 2508, Col San Pedro ZacatencoCDMX, C.P. 07360, Mexico City, Mexico.
Fluoride is emitted into the air not only through gas emissions but also from volcanic ash, leading to contact via inhalation. Therefore, the objective of the present study was to evaluate the cellular and biochemical responses in the A549 cell line after exposure to NaF (sodium fluoride) concentrations lower than those previously used in other studies to determine the impact on the lung epithelium. A549 cells were exposed to different concentrations (0.
View Article and Find Full Text PDFAlzheimers Dement (N Y)
December 2024
Eli Lilly and Company Indianapolis Indiana USA.
Introduction: The aggregation and spread of hyperphosphorylated, pathological tau in the human brain is hypothesized to play a key role in Alzheimer's disease (AD) as well as other neurogenerative tauopathies. O-GlcNAcylation, an important post-translational modification of tau and many other proteins, is significantly decreased in brain tissue of AD patients relative to healthy controls. Increased tau O-GlcNAcylation has been shown to reduce tau pathology in mouse in vivo tauopathy models.
View Article and Find Full Text PDFDiscov Oncol
December 2024
Clinical Medical College, North China University of Science and Technology, Tangshan, 063210, China.
Histone acetylation is an important epigenetic modification, modulating the development of many tumors. However, the functions of most histone acetylation-related genes (HARGs) and their prognostic values in Ewing sarcoma (EWS) remain unclear. The current study aimed to investigate the prognostic values and potential functions of HARGs in EWS.
View Article and Find Full Text PDFACS Omega
December 2024
Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5S 1P6, Canada.
Altered levels of intracellular protein glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) have emerged as being involved in various cancers and neurodegenerative diseases. OGA inhibitors have proven critically useful as tools to help understand the roles of O-GlcNAc, yet accessing large quantities of inhibitors necessary for many animal studies remains a challenge. Herein is described a scalable method to produce Thiamet-G, a potent, selective, and widely used brain-permeable OGA inhibitor.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Sarriena auzoa, 48940 Leioa, Spain.
Recurrent Pregnancy Loss (RPL), also named Recurrent Spontaneous Abortion (RSA), is a common fertility problem that refers to at least two consecutive pregnancy losses and affects 1-2% of couples all over the world. Despite common causes such as genetic abnormalities, uterine anomalies or hormonal and metabolic disorders, there is still a huge challenge in identifying the causes of about 40-60% of RPL patients. Circular RNAs (circRNAs) are endogenous ncRNAs with a unique closed-loop and single-stranded structure.
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