6AZT

Asparaginyl endopeptidase 1 bound to AAN peptide, a tetrahedral intermediate

6AZT の概要

• エントリーDOI: 10.2210/pdb6azt/pdb
• 分子名称: Asparaginyl endopeptidase 1, ALA-ALA-ASN tetrahedral intermediate, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: plant protein
• 由来する生物種: Helianthus annuus (Common sunflower); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54888.90

構造登録者

Bond, C.S. (登録日: 2017-09-13, 公開日: 2018-02-07, 最終更新日: 2023-11-15)

主引用文献

Haywood, J.,Schmidberger, J.W.,James, A.M.,Nonis, S.G.,Sukhoverkov, K.V.,Elias, M.,Bond, C.S.,Mylne, J.S.
Structural basis of ribosomal peptide macrocyclization in plants.
Elife, 7:-, 2018

PubMed Abstract: Constrained, cyclic peptides encoded by plant genes represent a new generation of drug leads. Evolution has repeatedly recruited the Cys-protease asparaginyl endopeptidase (AEP) to perform their head-to-tail ligation. These macrocyclization reactions use the substrates amino terminus instead of water to deacylate, so a peptide bond is formed. How solvent-exposed plant AEPs macrocyclize is poorly understood. Here we present the crystal structure of an active plant AEP from the common sunflower, . The active site contained electron density for a tetrahedral intermediate with partial occupancy that predicted a binding mode for peptide macrocyclization. By substituting catalytic residues we could alter the ratio of cyclic to acyclic products. Moreover, we showed AEPs from other species lacking cyclic peptides can perform macrocyclization under favorable pH conditions. This structural characterization of AEP presents a logical framework for engineering superior enzymes that generate macrocyclic peptide drug leads.

PubMed: 29384475
DOI: 10.7554/eLife.32955

実験手法

X-RAY DIFFRACTION (1.8 Å)