Exploring domain architectures of human glycosyltransferases: Highlighting the functional diversity of non-catalytic add-on domains

• Published in: Biochimica et biophysica acta. General subjects Vol. 1868; no. 10; p. 130687
• Main Authors: Yagi, Hirokazu, Takagi, Katsuki, Kato, Koichi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2024
• Subjects: active sites; Add-on domain; AlphaFold protein structure database; biosynthesis; Catalytic Domain; domain; enzyme activity; fibronectins; functional diversity; Glycosylation; Glycosyltransferase; glycosyltransferases; Glycosyltransferases - chemistry; Glycosyltransferases - metabolism; Humans; lectins; Models, Molecular; oligomerization; Polysaccharides - chemistry; Polysaccharides - metabolism; Protein Domains; protein structure; Substrate Specificity; therapeutics; Glycosyltransferase; Add-on domain; AlphaFold protein structure database
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2024.130687

Human glycosyltransferases (GTs) play crucial roles in glycan biosynthesis, exhibiting diverse domain architectures. This study explores the functional diversity of “add-on” domains within human GTs, using data from the AlphaFold Protein Structure Database. Among 215 annotated human GTs, 74 contain one or more add-on domains in addition to their catalytic domain. These domains include lectin folds, fibronectin type III, and thioredoxin-like domains and contribute to substrate specificity, oligomerization, and consequent enzymatic activity. Notably, certain GTs possess dual enzymatic functions due to catalytic add-on domains. The analysis highlights the importance of add-on domains in enzyme functionality and disease implications, such as congenital disorders of glycosylation. This comprehensive overview enhances our understanding of GT domain organization, providing insights into glycosylation mechanisms and potential therapeutic targets. •Human glycosyltransferase domain organization was comprehensively reviewed.•The human glycosyltransferases were classified by domain count and structural fold.•Structures and functions of the add-on domains in these enzymes were highlighted.