7V9N

Crystal structure of the lanthipeptide zinc-metallopeptidase EryP from saccharopolyspora erythraea in closed state

7V9N の概要

• エントリーDOI: 10.2210/pdb7v9n/pdb
• 分子名称: Alanine aminopeptidase, ZINC ION, CALCIUM ION, ... (6 entities in total)
• 機能のキーワード: aminopeptidase, alanine aminopeptidase, cytosolic protein, hydrolase
• 由来する生物種: Saccharopolyspora erythraea (strain ATCC 11635 / DSM 40517 / JCM 4748 / NBRC 13426 / NCIMB 8594 / NRRL 2338)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 98675.30

構造登録者

Zhao, C.,Zhao, N.L.,Bao, R. (登録日: 2021-08-26, 公開日: 2022-05-11, 最終更新日: 2024-05-29)

主引用文献

Zhao, C.,Sheng, W.,Wang, Y.,Zheng, J.,Xie, X.,Liang, Y.,Wei, W.,Bao, R.,Wang, H.
Conformational remodeling enhances activity of lanthipeptide zinc-metallopeptidases.
Nat.Chem.Biol., 18:724-732, 2022

PubMed Abstract: Lanthipeptides are an important group of natural products with diverse biological functions, and their biosynthesis requires the removal of N-terminal leader peptides (LPs) by designated proteases. LanP enzymes, a subgroup of M1 zinc-metallopeptidases, have been recently identified as bifunctional proteases with both endo- and aminopeptidase activities to remove LPs of class III and class IV lanthipeptides. Herein, we report the biochemical and structural characterization of EryP as the LanP enzyme from the biosynthesis of class III lanthipeptide erythreapeptin. We determined X-ray crystal structures of EryP in three conformational states, the open, intermediate and closed states, and identified a unique interdomain Ca binding site as a regulatory element that modulates its domain dynamics and proteolytic activity. Inspired by this regulatory Ca binding, we developed a strategy to engineer LanP enzymes for enhanced catalytic activities by strengthening interdomain associations and driving the conformational equilibrium toward their closed forms.

PubMed: 35513512
DOI: 10.1038/s41589-022-01018-2

実験手法

X-RAY DIFFRACTION (1.9 Å)