8A0F

Crystal structure of human deoxyhypusine synthase variant K329A in complex with NAD and SPD

8A0F の概要

• エントリーDOI: 10.2210/pdb8a0f/pdb
• 関連するPDBエントリー: 6XXJ 7A6S 7A6T 8A0E
• 分子名称: Deoxyhypusine synthase, SPERMIDINE, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: hypusination, transferase, posttranslational modification
• 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: 84122.77

構造登録者

Wator, E.,Wilk, P.,Grudnik, P. (登録日: 2022-05-27, 公開日: 2023-04-05, 最終更新日: 2024-11-20)

主引用文献

Wator, E.,Wilk, P.,Biela, A.,Rawski, M.,Zak, K.M.,Steinchen, W.,Bange, G.,Glatt, S.,Grudnik, P.
Cryo-EM structure of human eIF5A-DHS complex reveals the molecular basis of hypusination-associated neurodegenerative disorders.
Nat Commun, 14:1698-1698, 2023

PubMed Abstract: Hypusination is a unique post-translational modification of the eukaryotic translation factor 5A (eIF5A) that is essential for overcoming ribosome stalling at polyproline sequence stretches. The initial step of hypusination, the formation of deoxyhypusine, is catalyzed by deoxyhypusine synthase (DHS), however, the molecular details of the DHS-mediated reaction remained elusive. Recently, patient-derived variants of DHS and eIF5A have been linked to rare neurodevelopmental disorders. Here, we present the cryo-EM structure of the human eIF5A-DHS complex at 2.8 Å resolution and a crystal structure of DHS trapped in the key reaction transition state. Furthermore, we show that disease-associated DHS variants influence the complex formation and hypusination efficiency. Hence, our work dissects the molecular details of the deoxyhypusine synthesis reaction and reveals how clinically-relevant mutations affect this crucial cellular process.

PubMed: 36973244
DOI: 10.1038/s41467-023-37305-2

実験手法

X-RAY DIFFRACTION (1.64 Å)