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Abstract
Modification of specific Ser and Thr residues of nucleocytoplasmic proteins with O-GlcNAc, catalyzed by O-GlcNAc transferase (OGT), is an abundant posttranslational event essential for proper animal development and is dysregulated in various diseases. Due to the rapid concurrent removal by the single O-GlcNAcase (OGA), precise functional dissection of site-specific O-GlcNAc modification in vivo is currently not possible without affecting the entire O-GlcNAc proteome. Exploiting the fortuitous promiscuity of OGT, we show that S-GlcNAc is a hydrolytically stable and accurate structural mimic of O-GlcNAc that can be encoded in mammalian systems with CRISPR-Cas9 in an otherwise unperturbed O-GlcNAcome. Using this approach, we target an elusive Ser 405 O-GlcNAc site on OGA, showing that this site-specific modification affects OGA stability.
Original language | English |
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Pages (from-to) | 1071-1077 |
Number of pages | 7 |
Journal | Nature Structural & Molecular Biology |
Volume | 26 |
Issue number | 11 |
Early online date | 6 Nov 2019 |
DOIs | |
Publication status | Published - Nov 2019 |
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology
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