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 Cited by 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: 29051530DOI: 10.1038/s41467-017-00862-4 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (2.19 Å) |
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