6JJO

Crystal structure of the DegP dodecamer with a modulator

6JJO の概要

• エントリーDOI: 10.2210/pdb6jjo/pdb
• 分子名称: Periplasmic serine endoprotease DegP, TMB-CYRKL modulator (2 entities in total)
• 機能のキーワード: protease, hydrolase
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 303139.19

構造登録者

Cho, H.,Choi, Y.,Lee, H.H.,Kim, S. (登録日: 2019-02-26, 公開日: 2020-09-02, 最終更新日: 2023-11-22)

主引用文献

Cho, H.,Choi, Y.,Min, K.,Son, J.B.,Park, H.,Lee, H.H.,Kim, S.
Over-activation of a nonessential bacterial protease DegP as an antibiotic strategy
Commun Biol, 3:547-547, 2020

PubMed Abstract: Rising antibiotic resistance urgently begs for novel targets and strategies for antibiotic discovery. Here, we report that over-activation of the periplasmic DegP protease, a member of the highly conserved HtrA family, can be a viable strategy for antibiotic development. We demonstrate that tripodal peptidyl compounds that mimic DegP-activating lipoprotein variants allosterically activate DegP and inhibit the growth of an Escherichia coli strain with a permeable outer membrane in a DegP-dependent fashion. Interestingly, these compounds inhibit bacterial growth at a temperature at which DegP is not essential for cell viability, mainly by over-proteolysis of newly synthesized proteins. Co-crystal structures show that the peptidyl arms of the compounds bind to the substrate-binding sites of DegP. Overall, our results represent an intriguing example of killing bacteria by activating a non-essential enzyme, and thus expand the scope of antibiotic targets beyond the traditional essential proteins or pathways.

PubMed: 33005001
DOI: 10.1038/s42003-020-01266-9

実験手法

X-RAY DIFFRACTION (4.157 Å)