9CX8

Crystal structure of Human FN3K in apo-state

9CX8 の概要

• エントリーDOI: 10.2210/pdb9cx8/pdb
• 分子名称: Fructosamine-3-kinase, SULFATE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: kinase, apo-state, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68067.26

構造登録者

Garg, A.,On, K.F.,Joshua-Tor, L. (登録日: 2024-07-30, 公開日: 2024-12-18, 最終更新日: 2025-02-05)

主引用文献

Garg, A.,On, K.F.,Xiao, Y.,Elkayam, E.,Cifani, P.,David, Y.,Joshua-Tor, L.
The molecular basis of Human FN3K mediated phosphorylation of glycated substrates.
Nat Commun, 16:941-941, 2025

PubMed Abstract: Glycation, a non-enzymatic post-translational modification occurring on proteins, can be actively reversed via site-specific phosphorylation of the fructose-lysine moiety by FN3K kinase, to impact the cellular function of the target protein. A regulatory axis between FN3K and glycated protein targets has been associated with conditions like diabetes and cancer. However, the molecular basis of this relationship has not been explored so far. Here, we determined a series of crystal structures of HsFN3K in the apo-state, and in complex with different nucleotide analogs together with a sugar substrate mimic to reveal the features important for its kinase activity and substrate recognition. Additionally, the dynamics in sugar substrate binding during the kinase catalytic cycle provide important mechanistic insights into HsFN3K function. Our structural work provides the molecular basis for rational small molecule design targeting FN3K.

PubMed: 39843453
DOI: 10.1038/s41467-025-56207-z

実験手法

X-RAY DIFFRACTION (1.67 Å)