9WJK

Crystal structure of mouse EOGT-UDP complex

Summary for 9WJK

• Entry DOI: 10.2210/pdb9wjk/pdb
• Descriptor: EGF domain-specific O-linked N-acetylglucosamine transferase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: o-glcnac, glycosyltransferase, er protein, transferase
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 59169.55

Authors

Nagae, M.,Tashima, Y.,Okajima, T. (deposition date: 2025-08-31, release date: 2026-05-27)

Primary citation

Tashima, Y.,Nagae, M.,Jiang, J.,Okajima, T.
Crystal structure of epidermal growth factor domain-specific O -linked N -acetylglucosamine transferase reveals a conserved N-R-R constellation for uridine diphosphate recognition in the GT61 family.
Pnas Nexus, 5:pgag115-pgag115, 2026

PubMed Abstract: Epidermal growth factor (EGF) domain-specific -linked -acetylglucosamine transferase (EOGT), a glycosyltransferase (GT) 61 family member, catalyzes --acetylglucosamine (-GlcNAc) transfer from uridine diphosphate (UDP)-GlcNAc to serine or threonine residues within EGF domains in the endoplasmic reticulum. In this study, we determined the crystal structure of the EOGT-UDP complex and identified the critical residues mediating their interactions, which were validated via site-directed mutagenesis and enzyme activity assays. These residues were conserved in EOGT orthologs across metazoans, and UDP binding occurred independently of divalent metal ions and the canonical Asp-X-Asp motif. Although EOGT catalyzes -GlcNAcylation, similar to -GlcNAc transferase (OGT), it shares little sequence similarity with OGT and belongs to a distinct GT family. Instead, EOGT is more closely related to protein -linked-mannose β1,4--acetylglucosaminyltransferase 2 (POMGNT2). Structural comparison with POMGNT2 revealed a conserved triad of one asparagine and two arginine residues, the N-R-R constellation. These elements were conserved across metazoans and green plants (Viridiplantae), suggesting a unifying mechanism of UDP recognition and providing a framework to interpret disease-associated mutations and assess the evolution of catalytically active GT61 family enzymes.

PubMed: 42058885
DOI: 10.1093/pnasnexus/pgag115

Experimental method

X-RAY DIFFRACTION (1.8 Å)