8ACR

Structure of Pseudomonas aeruginosa aminopeptidase, PaAP

8ACR の概要

• エントリーDOI: 10.2210/pdb8acr/pdb
• 分子名称: Keratinase KP1, ZINC ION, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: e340a mutant, full-length, hydrolase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55102.10

構造登録者

Harding, C.J.,Czekster, C.M. (登録日: 2022-07-06, 公開日: 2023-07-12, 最終更新日: 2024-11-06)

主引用文献

Harding, C.J.,Bischoff, M.,Bergkessel, M.,Czekster, C.M.
An anti-biofilm cyclic peptide targets a secreted aminopeptidase from P. aeruginosa.
Nat.Chem.Biol., 19:1158-1166, 2023

PubMed Abstract: Pseudomonas aeruginosa is an opportunistic pathogen that causes serious illness, especially in immunocompromised individuals. P. aeruginosa forms biofilms that contribute to growth and persistence in a wide range of environments. Here we investigated the aminopeptidase, P. aeruginosa aminopeptidase (PaAP) from P. aeruginosa, which is highly abundant in the biofilm matrix. PaAP is associated with biofilm development and contributes to nutrient recycling. We confirmed that post-translational processing was required for activation and PaAP is a promiscuous aminopeptidase acting on unstructured regions of peptides and proteins. Crystal structures of wild-type enzymes and variants revealed the mechanism of autoinhibition, whereby the C-terminal propeptide locks the protease-associated domain and the catalytic peptidase domain into a self-inhibited conformation. Inspired by this, we designed a highly potent small cyclic-peptide inhibitor that recapitulates the deleterious phenotype observed with a PaAP deletion variant in biofilm assays and present a path toward targeting secreted proteins in a biofilm context.

PubMed: 37386135
DOI: 10.1038/s41589-023-01373-8

実験手法

X-RAY DIFFRACTION (2.1 Å)