5N4C

Prolyl oligopeptidase B from Galerina marginata bound to 35mer hydrolysis and macrocyclization substrate - S577A mutant

5N4C の概要

• エントリーDOI: 10.2210/pdb5n4c/pdb
• 分子名称: Prolyl oligopeptidase, Alpha-amanitin proprotein, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: amanitin biosynthesis, prolyl oligopeptidase, macrocyclase, peptidase, beta-propeller, closed form, hydrolase
• 由来する生物種: Galerina marginata; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 342935.61

構造登録者

Czekster, C.M.,McMahon, S.A.,Ludewig, H.,Naismith, J.H. (登録日: 2017-02-10, 公開日: 2017-11-01, 最終更新日: 2024-05-08)

主引用文献

Czekster, C.M.,Ludewig, H.,McMahon, S.A.,Naismith, J.H.
Characterization of a dual function macrocyclase enables design and use of efficient macrocyclization substrates.
Nat Commun, 8:1045-1045, 2017

PubMed Abstract: Peptide macrocycles are promising therapeutic molecules because they are protease resistant, structurally rigid, membrane permeable, and capable of modulating protein-protein interactions. Here, we report the characterization of the dual function macrocyclase-peptidase enzyme involved in the biosynthesis of the highly toxic amanitin toxin family of macrocycles. The enzyme first removes 10 residues from the N-terminus of a 35-residue substrate. Conformational trapping of the 25 amino-acid peptide forces the enzyme to release this intermediate rather than proceed to macrocyclization. The enzyme rebinds the 25 amino-acid peptide in a different conformation and catalyzes macrocyclization of the N-terminal eight residues. Structures of the enzyme bound to both substrates and biophysical analysis characterize the different binding modes rationalizing the mechanism. Using these insights simpler substrates with only five C-terminal residues were designed, allowing the enzyme to be more effectively exploited in biotechnology.

PubMed: 29051530
DOI: 10.1038/s41467-017-00862-4

実験手法

X-RAY DIFFRACTION (2.19 Å)