Site-specific prediction of O-GlcNAc modification in proteins using evolutionary scale model DOI Creative Commons
Ayesha Khalid, Afshan Kaleem, Wajahat M. Qazi

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(12), P. e0316215 - e0316215

Published: Dec. 31, 2024

Protein glycosylation, a vital post-translational modification, is pivotal in various biological processes and disease pathogenesis. Computational approaches, including protein language models machine learning algorithms, have emerged as valuable tools for predicting O- GlcNAc sites, reducing experimental costs, enhancing efficiency. However, the literature has not reported prediction of O -GlcNAc sites through evolutionary scale model (ESM). Therefore, this study employed ESM-2 site humans. Approximately 1100 - linked glycoprotein sequences retrieved from database were utilized training. The exhibited consistent improvement over epochs, achieving an accuracy 78.30%, recall precision 61.31%, F1-score 68.74%. compared to traditional which show overfitting on same data up 99%, outperforms terms optimal training testing predictions. These findings underscore effectiveness accurately within human proteins. Accurately proteins can significantly advance glycoproteomic research by our understanding function mechanisms, aiding developing targeted therapies, facilitating biomarker discovery improved diagnosis treatment. Furthermore, future studies should focus more diverse types, longer sequence lengths, higher computational resources evaluate parameters. Accurate might enhance investigation site-specific functions physiology diseases.

Language: Английский

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease DOI Open Access
Érica Novaes Soares, Ana Carla dos Santos Costa,

Gabriel de Jesus Ferrolho

et al.

Published: Jan. 31, 2024

Parkinson’s disease (PD) is a progressive neurodegenerative characterized by resting tremor, bradykinesia, rigidity, postural instability, that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) the primary neurotransmitter involved in this disease, but cholinergic imbalance has been implicated. Current intervention PD focused on replenishing central DA, which provides remarkable temporary symptomatic relief does not address neuronal losss and progression of disease. It well established nicotinic receptors (nAChRs) can regulate DA release nicotine itself may have neuroprotective effects. Recent studies identified nAChRs nonneuronal cell types including glial cells, where they inflammatory responses. Given crucial role neuroinflammation dopaminergic degeneration, involvement microglia astrocytes response, provide novel therapeutic target prevention and/or treatment PD. In review, following brief discussion PD, we focus cells specifically their pathology treatment.

Language: Английский

Citations

5
Mapping O- and N-Glycosylation in Transmembrane and Interface Regions of Proteins: Insights from a Database Search Study DOI Open Access

Giorgiana Diana Carmen Anghelescu,

Maria Mernea, Dan Mihăilescu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 327 - 327

Published: Jan. 2, 2025

Glycosylation is a critical post-translational modification that influences protein folding, stability and function. While extensively studied in extracellular intracellular regions, glycosylation within transmembrane (TM) regions at membrane interfaces remains poorly understood. This study aimed to map O- N-glycosylation sites these using comprehensive database search structural validation where possible. Extensive searches revealed range of proteins. Only the falling TM interface (according Uniprot annotations) were retained. The location was confirmed based on available 3D structures. We identified 32 O-glycosylation 7 domains 29 O-GlcNAc validated as located presented side chains either oriented toward lipid bilayer or buried protein. predicted largely confined domains. results obtained here highlight occurrence proteins interfaces. dataset provides valuable foundation for further exploration functional roles membrane-associated regions.

Language: Английский

Citations

0
O-GlcNAcylation: A Major Nutrient/Stress Sensor that Regulates Cellular Physiology DOI Creative Commons
Lance Wells, Gerald W. Hart

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(9), P. 107635 - 107635

Published: Aug. 5, 2024

Language: Английский

Citations

3
Selective bioorthogonal probe for N-glycan hybrid structures DOI
M. Mukherjee,

Devin Biesbrock,

Lara K. Abramowitz

et al.

Nature Chemical Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 28, 2024

Language: Английский

Citations

2
O-GlcNAc informatics: advances and trends DOI
Chunyan Hou, Weiyu Li, Yaoxiang Li

et al.

Analytical and Bioanalytical Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Language: Английский

Citations

2
Golgi defect as a major contributor to lysosomal dysfunction DOI Creative Commons

Sarah Reem Akaaboune,

Yanzhuang Wang

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: April 24, 2024

The Golgi apparatus plays a crucial role in lysosome biogenesis and the delivery of lysosomal enzymes, essential for maintaining cellular homeostasis ensuring cell survival. Deficiencies structure function can profoundly impact homeostasis, leading to various storage diseases neurodegenerative disorders. In this review, we highlight Reassembly Stacking Proteins (GRASPs) formation apparatus, emphasizing current understanding association between lysosomes, diseases. Additionally, discuss how dysfunction leads secretion enzymes. This review aims serve as concise resource, offering insights into structure, function, disease-related defects, their consequential effects on function. By highlighting defects an underappreciated contributor across diseases, aim enhance comprehension these intricate processes.

Language: Английский

Citations

1
Decoding the Role of O-GlcNAcylation in Hepatocellular Carcinoma DOI Creative Commons
Xinyu Zhou,

Sirui Hang,

Qingqing Wang

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(8), P. 908 - 908

Published: July 25, 2024

Post-translational modifications (PTMs) influence protein functionality by modulating stability, localization, and interactions with other molecules, thereby controlling various cellular processes. Common PTMs include phosphorylation, acetylation, ubiquitination, glycosylation, SUMOylation, methylation, sulfation, nitrosylation. Among these modifications, O-GlcNAcylation has been shown to play a critical role in cancer development progression, especially hepatocellular carcinoma (HCC). This review outlines the of progression HCC. Moreover, we delve into underlying mechanisms HCC highlight compounds that target O-GlcNAc transferase (OGT) O-GlcNAcase (OGA) improve treatment outcomes. Understanding will offer insights potential therapeutic strategies targeting OGT OGA, which could for patients

Language: Английский

Citations

1
The Possible Roles of Glucosamine-6-Phosphate Deaminases in Ammonium Metabolism in Cancer DOI Open Access

Roberto Lara‐Lemus,

Manuel Castillejos‐López, Arnoldo Aquino‐Gálvez

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12054 - 12054

Published: Nov. 9, 2024

Nearly 5% of the glucose-6-phosphate (Glc6P) in cells is diverted into hexosamine biosynthetic pathway (HBP) to synthesize glucosamine-6-phosphate (GlcN6P) and uridine diphosphate

Language: Английский

Citations

0
O-glycosylation is essential for cell surface expression of the transcobalamin receptor CD320 DOI Creative Commons

Chunyu Du,

Wenjun Guo, Mengting Wang

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(12), P. 107997 - 107997

Published: Nov. 16, 2024

CD320 is a cell surface receptor that mediates vitamin B12 uptake in most tissues. To date, the mechanisms regulate expression on are not fully understood. In this work, we studied transfected human embryonic kidney (HEK) 293 and hepatoma HepG2 cells. By glycosidase trypsin digestion, monensin brefeldin treatment, western blotting, flow cytometry, lectin binding, found underwent N- O-glycosylation sialylation, resulting ∼70-kDa band formed high-molecular-weight complex surface. Site-directed mutagenesis altering Asn126, Asn195, Asn213 residues, individually or together, abolished N-glycosylation but did block its intracellular trafficking HEK293 contrast, treatment of cells with Ben-gal, structural analog GalNAc-α-1-O-Ser/Thr, inhibited decreased uptake. Analysis deletion mutants indicated sites Ser/Thr-rich region near transmembrane domain were important for These results reveal an role O-glycans, N-glycans, CD320, providing new insights into cellular regulating function metabolism.

Language: Английский

Citations

0
O-GlcNAcylation modulates expression and abundance of N-glycosylation machinery in an inherited glycosylation disorder DOI Creative Commons

Courtney Matheny-Rabun,

Sneha S. Mokashi, Silvia Radenkovic

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(11), P. 114976 - 114976

Published: Nov. 1, 2024

Core components of the N-glycosylation pathway are known, but metabolic and post-translational mechanisms regulating this in normal disease states remain elusive. Using a multi-omic approach zebrafish, we discovered mechanism whereby O-GlcNAcylation directly impacts expression abundance two rate-limiting proteins N-linked glycosylation pathway. We show model an inherited disorder PMM2-CDG, congenital disorders that phosphomannomutase deficiency is associated with increased levels UDP-GlcNAc protein O-GlcNAcylation. O-GlcNAc modification increases transcript both NgBR Dpagt1 pmm2

Language: Английский

Citations

0