7PX8

CryoEM structure of mammalian acylaminoacyl-peptidase

7PX8 の概要

• エントリーDOI: 10.2210/pdb7px8/pdb
• EMDBエントリー: 13691
• 分子名称: Acylamino-acid-releasing enzyme (1 entity in total)
• 機能のキーワード: acylaminoacyl-peptidase, tetramer, aclypeptide-hydrolase, oxidized protein hydrolase, serine-protease, hydrolase
• 由来する生物種: Sus scrofa domesticus (domestic pig)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 325297.56

構造登録者

Kiss-Szeman, A.J.,Harmat, V.,Menyhard, D.K.,Straner, P.,Jakli, I.,Hosogi, N.,Perczel, A. (登録日: 2021-10-08, 公開日: 2022-05-25, 最終更新日: 2025-07-09)

主引用文献

Kiss-Szeman, A.J.,Straner, P.,Jakli, I.,Hosogi, N.,Harmat, V.,Menyhard, D.K.,Perczel, A.
Cryo-EM structure of acylpeptide hydrolase reveals substrate selection by multimerization and a multi-state serine-protease triad.
Chem Sci, 13:7132-7142, 2022

PubMed Abstract: The first structure of tetrameric mammalian acylaminoacyl peptidase, an enzyme that functions as an upstream regulator of the proteasome through the removal of terminal -acetylated residues from its protein substrates, was determined by cryo-EM and further elucidated by MD simulations. Self-association results in a toroid-shaped quaternary structure, guided by an amyloidogenic β-edge and unique inserts. With a Pro introduced into its central β-sheet, sufficient conformational freedom is awarded to the segment containing the catalytic Ser587 that the serine protease catalytic triad alternates between active and latent states. Active site flexibility suggests that the dual function of catalysis and substrate selection are fulfilled by a novel mechanism: substrate entrance is regulated by flexible loops creating a double-gated channel system, while binding of the substrate to the active site is required for stabilization of the catalytic apparatus - as a second filter before hydrolysis. The structure not only underlines that within the family of S9 proteases homo-multimerization acts as a crucial tool for substrate selection, but it will also allow drug design targeting of the ubiquitin-proteasome system.

PubMed: 35799812
DOI: 10.1039/d2sc02276a

実験手法

ELECTRON MICROSCOPY (3.27 Å)