8KHG

Itaconyl-CoA hydratase PaIch

8KHG の概要

• エントリーDOI: 10.2210/pdb8khg/pdb
• 分子名称: Itaconyl-CoA hydratase, CITRIC ACID (3 entities in total)
• 機能のキーワード: itaconyl-coa hydratase, unknown function
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61509.03

構造登録者

Huang, Q.,Bao, R. (登録日: 2023-08-21, 公開日: 2024-05-15, 最終更新日: 2024-07-24)

主引用文献

Huang, Q.,Duan, C.,Ma, H.,Nong, C.,Zheng, Q.,Zhou, J.,Zhao, N.,Mou, X.,Liu, T.,Zou, S.,Yang, N.,Tong, A.,Qin, W.,Bao, R.
Structural and functional characterization of itaconyl-CoA hydratase and citramalyl-CoA lyase involved in itaconate metabolism of Pseudomonas aeruginosa.
Structure, 32:941-952.e3, 2024

PubMed Abstract: Itaconate is a key anti-inflammatory/antibacterial metabolite in pathogen-macrophage interactions that induces adaptive changes in Pseudomonas aeruginosa-exposed airways. However, the impact and mechanisms underlying itaconate metabolism remain unclear. Our study reveals that itaconate significantly upregulates the expression of pyoverdine in P. aeruginosa and enhances its tolerance to tobramycin. Notably, the enzymes responsible for efficient itaconate metabolism, PaIch and PaCcl, play crucial roles in both utilizing itaconate and clearing its toxic metabolic intermediates. By using protein crystallography and molecular dynamics simulations analyses, we have elucidated the unique catalytic center and substrate-binding pocket of PaIch, which contribute to its highly efficient catalysis. Meanwhile, analysis of PaCcl has revealed how interactions between domains regulate the conformational changes of the active sites and binding pockets, influencing the catalytic process. Overall, our research uncovers the significance and mechanisms of PaIch and PaCcl in the efficient metabolism of itaconate by P. aeruginosa.

PubMed: 38677288
DOI: 10.1016/j.str.2024.04.004

実験手法

X-RAY DIFFRACTION (2.6 Å)