6RHE

CpOGA D298N in complex with hOGA-derived S-GlcNAc peptide

Summary for 6RHE

• Entry DOI: 10.2210/pdb6rhe/pdb
• Descriptor: O-GlcNAcase NagJ, ACE-ALA-HIS-CYS-GLY-NH2, CADMIUM ION, ... (5 entities in total)
• Functional Keywords: n-acetyl glucosamine, hydrolase
• Biological source: Clostridium perfringens ATCC 13124; More
• Total number of polymer chains: 2
• Total formula weight: 69791.22

Authors

Van Aalten, D.,Bartual, S.G.,Gorelik, A. (deposition date: 2019-04-19, release date: 2019-12-25, Last modification date: 2024-10-16)

Primary citation

Gorelik, A.,Bartual, S.G.,Borodkin, V.S.,Varghese, J.,Ferenbach, A.T.,van Aalten, D.M.F.
Genetic recoding to dissect the roles of site-specific protein O-GlcNAcylation.
Nat.Struct.Mol.Biol., 26:1071-1077, 2019

PubMed 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.

PubMed: 31695185
DOI: 10.1038/s41594-019-0325-8

Experimental method

X-RAY DIFFRACTION (3.1 Å)