4RE6

Acylaminoacyl peptidase complexed with a chloromethylketone inhibitor

4RE6 の概要

• エントリーDOI: 10.2210/pdb4re6/pdb
• 関連するPDBエントリー: 4RE5
• 関連するBIRD辞書のPRD_ID: PRD_001053
• 分子名称: Acylamino-acid-releasing enzyme, N-[(benzyloxy)carbonyl]glycyl-N-[(2S,3R)-4-chloro-3-hydroxy-1-phenylbutan-2-yl]glycinamide, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: beta-propeller, alpha-beta-hydrolase fold, chloromethyl-ketone inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Aeropyrum pernix
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 253542.75

構造登録者

Menyhard, D.K.,Orgovan, Z.,Szeltner, Z.,Szamosi, I.,Harmat, V. (登録日: 2014-09-22, 公開日: 2015-01-28, 最終更新日: 2024-11-20)

主引用文献

Menyhard, D.K.,Orgovan, Z.,Szeltner, Z.,Szamosi, I.,Harmat, V.
Catalytically distinct states captured in a crystal lattice: the substrate-bound and scavenger states of acylaminoacyl peptidase and their implications for functionality.
Acta Crystallogr.,Sect.D, 71:461-472, 2015

PubMed Abstract: Acylaminoacyl peptidase (AAP) is an oligopeptidase that only cleaves short peptides or protein segments. In the case of AAP from Aeropyrum pernix (ApAAP), previous studies have led to a model in which the clamshell-like opening and closing of the enzyme provides the means of substrate-size selection. The closed form of the enzyme is catalytically active, while opening deactivates the catalytic triad. The crystallographic results presented here show that the open form of ApAAP is indeed functionally disabled. The obtained crystal structures also reveal that the closed form is penetrable to small ligands: inhibitor added to the pre-formed crystal was able to reach the active site of the rigidified protein, which is only possible through the narrow channel of the propeller domain. Molecular-dynamics simulations investigating the structure of the complexes formed with longer peptide substrates showed that their binding within the large crevice of the closed form of ApAAP leaves the enzyme structure unperturbed; however, their accessing the binding site seems more probable when assisted by opening of the enzyme. Thus, the open form of ApAAP corresponds to a scavenger of possible substrates, the actual cleavage of which only takes place if the enzyme is able to re-close.

PubMed: 25760596
DOI: 10.1107/S1399004714026819

実験手法

X-RAY DIFFRACTION (2.55 Å)