6rhe

Publication Abstract from PubMed

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.

Genetic recoding to dissect the roles of site-specific protein O-GlcNAcylation.,Gorelik A, Bartual SG, Borodkin VS, Varghese J, Ferenbach AT, van Aalten DMF Nat Struct Mol Biol. 2019 Nov;26(11):1071-1077. doi: 10.1038/s41594-019-0325-8., Epub 2019 Nov 6. PMID:31695185^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.