9NE4

cryoEM structure of the A-chain of the human OGA-L Catalytic Dimer

9NE4 の概要

• エントリーDOI: 10.2210/pdb9ne4/pdb
• EMDBエントリー: 49293 49294
• 分子名称: Protein O-GlcNAcase (1 entity in total)
• 機能のキーワード: o-glcnac, histones, dna repair, dna damage, transcription, epigenetics, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 103020.91

構造登録者

Nyenhuis, S.B.,Steenackers, A.,Hinshaw, J.E.,Hanover, J.A. (登録日: 2025-02-19, 公開日: 2025-12-24, 最終更新日: 2026-01-14)

主引用文献

Nyenhuis, S.B.,Steenackers, A.,Mukherjee, M.M.,Hinshaw, J.E.,Hanover, J.A.
Human O-GlcNAcase catalytic-stalk dimer anchors flexible histone binding domains.
Commun Chem, 9:8-8, 2025

PubMed Abstract: Although thousands of proteins are specifically O-GlcNAc modified, the molecular features recognized by the enzymes of O-GlcNAc cycling (OGT/OGA) remain poorly defined. Here we solved the structure of the long isoform of human OGA (OGA-L) by cryo-electron microscopy (cryo-EM) providing a physiologically relevant platform to study the enzyme. The catalytic-stalk dimer structure was solved to a resolution of 3.63 Å, and the locally refined OGA A- and B-chains to 2.98 Å and 3.05 Å respectively. Intriguingly, the cryo-EM structures also exhibit lower resolution densities associated with the pHAT domains, suggesting substantial flexion of these domains relative to the catalytic-stalk dimer. OGA-L binds to a small subset of the 384 modified histone tails on a commercial histone peptide array. High affinity binding of OGA-L was detected to recombinant DNA-containing mononucleosomes bearing the H3K36 and H4K modifications. The OGA-L-H3K36 interaction was further validated by traditional ChIP experiments in MEFs. Thus, OGA-L binds to two modified histone tails of nucleosomes linked to open chromatin, whereas it does not bind to marks associated with repressive chromatin. This model is consistent with OGA-L acting as a 'reader' of histone modifications linked to development, transcriptional activation, transposon silencing, and DNA damage repair.

PubMed: 41366547
DOI: 10.1038/s42004-025-01813-7

実験手法

ELECTRON MICROSCOPY (2.98 Å)