7XMC

Cryo-EM structure of Cytochrome bo3 from Escherichia coli, apo structure with DMSO

7XMC の概要

• エントリーDOI: 10.2210/pdb7xmc/pdb
• EMDBエントリー: 33293
• 分子名称: Cytochrome bo(3) ubiquinol oxidase subunit 1, Ubiquinol oxidase subunit 2, Cytochrome bo(3) ubiquinol oxidase subunit 3, ... (9 entities in total)
• 機能のキーワード: respiratory enzyme, membrane protein, heme protein, apo structure, oxidoreductase
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 149064.98

構造登録者

Nishida, Y.,Shigematsu, H.,Iwamoto, T.,Takashima, S.,Shintani, Y. (登録日: 2022-04-25, 公開日: 2022-12-21, 最終更新日: 2024-07-03)

主引用文献

Nishida, Y.,Yanagisawa, S.,Morita, R.,Shigematsu, H.,Shinzawa-Itoh, K.,Yuki, H.,Ogasawara, S.,Shimuta, K.,Iwamoto, T.,Nakabayashi, C.,Matsumura, W.,Kato, H.,Gopalasingam, C.,Nagao, T.,Qaqorh, T.,Takahashi, Y.,Yamazaki, S.,Kamiya, K.,Harada, R.,Mizuno, N.,Takahashi, H.,Akeda, Y.,Ohnishi, M.,Ishii, Y.,Kumasaka, T.,Murata, T.,Muramoto, K.,Tosha, T.,Shiro, Y.,Honma, T.,Shigeta, Y.,Kubo, M.,Takashima, S.,Shintani, Y.
Identifying antibiotics based on structural differences in the conserved allostery from mitochondrial heme-copper oxidases.
Nat Commun, 13:7591-7591, 2022

PubMed Abstract: Antimicrobial resistance (AMR) is a global health problem. Despite the enormous efforts made in the last decade, threats from some species, including drug-resistant Neisseria gonorrhoeae, continue to rise and would become untreatable. The development of antibiotics with a different mechanism of action is seriously required. Here, we identified an allosteric inhibitory site buried inside eukaryotic mitochondrial heme-copper oxidases (HCOs), the essential respiratory enzymes for life. The steric conformation around the binding pocket of HCOs is highly conserved among bacteria and eukaryotes, yet the latter has an extra helix. This structural difference in the conserved allostery enabled us to rationally identify bacterial HCO-specific inhibitors: an antibiotic compound against ceftriaxone-resistant Neisseria gonorrhoeae. Molecular dynamics combined with resonance Raman spectroscopy and stopped-flow spectroscopy revealed an allosteric obstruction in the substrate accessing channel as a mechanism of inhibition. Our approach opens fresh avenues in modulating protein functions and broadens our options to overcome AMR.

PubMed: 36481732
DOI: 10.1038/s41467-022-34771-y

実験手法

ELECTRON MICROSCOPY (3.09 Å)