8PUT

IF5A in complex with Deoxyhypusine synthase

8PUT の概要

• エントリーDOI: 10.2210/pdb8put/pdb
• 分子名称: Probable deoxyhypusine synthase, Translation initiation factor 5A, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: lysine modification, hypusine, translation, eif5a
• 由来する生物種: Sulfolobus islandicus; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 201261.03

構造登録者

Ennifar, E.,D'agostino, M. (登録日: 2023-07-17, 公開日: 2024-07-03, 最終更新日: 2024-07-24)

主引用文献

D'Agostino, M.,Simonetti, A.,Motta, S.,Wolff, P.,Romagnoli, A.,Piccinini, A.,Spinozzi, F.,Di Marino, D.,La Teana, A.,Ennifar, E.
Crystal structure of archaeal IF5A-DHS complex reveals insights into the hypusination mechanism.
Structure, 32:878-, 2024

PubMed Abstract: The translation factor IF5A is highly conserved in Eukarya and Archaea and undergoes a unique post-translational hypusine modification by the deoxyhypusine synthase (DHS) enzyme. DHS transfers the butylamine moiety from spermidine to IF5A using NAD as a cofactor, forming a deoxyhypusine intermediate. IF5A is a key player in protein synthesis, preventing ribosome stalling in proline-rich sequences during translation elongation and facilitating translation elongation and termination. Additionally, human eIF5A participates in various essential cellular processes and contributes to cancer metastasis, with inhibiting hypusination showing anti-proliferative effects. The hypusination pathway of IF5A is therefore an attractive new therapeutic target. We elucidated the 2.0 Å X-ray crystal structure of the archaeal DHS-IF5A complex, revealing hetero-octameric architecture and providing a detailed view of the complex active site including the hypusination loop. This structure, along with biophysical data and molecular dynamics simulations, provides new insights into the catalytic mechanism of the hypusination reaction.

PubMed: 38582076
DOI: 10.1016/j.str.2024.03.008

実験手法

X-RAY DIFFRACTION (2 Å)