5O3W

Structural characterization of the fast and promiscuous macrocyclase from plant - PCY1-S562A bound to Presegetalin A1

5O3W の概要

• エントリーDOI: 10.2210/pdb5o3w/pdb
• 分子名称: Peptide cyclase 1, Presegetalin A1, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: segetalin biosynthesis, prolyl oligopeptidase, macrocyclase, peptidase, beta-propeller, closed form, hydrolase
• 由来する生物種: Vaccaria hispanica; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 343793.43

構造登録者

Ludewig, H.,Czekster, C.M.,Bent, A.F.,Naismith, J.H. (登録日: 2017-05-25, 公開日: 2018-02-07, 最終更新日: 2024-05-01)

主引用文献

Ludewig, H.,Czekster, C.M.,Oueis, E.,Munday, E.S.,Arshad, M.,Synowsky, S.A.,Bent, A.F.,Naismith, J.H.
Characterization of the Fast and Promiscuous Macrocyclase from Plant PCY1 Enables the Use of Simple Substrates.
ACS Chem. Biol., 13:801-811, 2018

PubMed Abstract: Cyclic ribosomally derived peptides possess diverse bioactivities and are currently of major interest in drug development. However, it can be chemically challenging to synthesize these molecules, hindering the diversification and testing of cyclic peptide leads. Enzymes used in vitro offer a solution to this; however peptide macrocyclization remains the bottleneck. PCY1, involved in the biosynthesis of plant orbitides, belongs to the class of prolyl oligopeptidases and natively displays substrate promiscuity. PCY1 is a promising candidate for in vitro utilization, but its substrates require an 11 to 16 residue C-terminal recognition tail. We have characterized PCY1 both kinetically and structurally with multiple substrate complexes revealing the molecular basis of recognition and catalysis. Using these insights, we have identified a three residue C-terminal extension that replaces the natural recognition tail permitting PCY1 to operate on synthetic substrates. We demonstrate that PCY1 can macrocyclize a variety of substrates with this short tail, including unnatural amino acids and nonamino acids, highlighting PCY1's potential in biocatalysis.

PubMed: 29377663
DOI: 10.1021/acschembio.8b00050

実験手法

X-RAY DIFFRACTION (2 Å)