5B1O

DHp domain structure of EnvZ P248A mutant

5B1O の概要

• エントリーDOI: 10.2210/pdb5b1o/pdb
• 関連するPDBエントリー: 5B1N
• 分子名称: Osmolarity sensor protein EnvZ (2 entities in total)
• 機能のキーワード: two-component system, autophosphorylation, dhp domain, histidine kinase, signaling protein
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15391.53

構造登録者

Okajima, T.,Eguchi, Y.,Tochio, N.,Inukai, Y.,Shimizu, R.,Ueda, S.,Shinya, S.,Kigawa, T.,Fukamizo, T.,Igarashi, M.,Utsumi, R. (登録日: 2015-12-09, 公開日: 2016-12-14, 最終更新日: 2023-11-08)

主引用文献

Eguchi, Y.,Okajima, T.,Tochio, N.,Inukai, Y.,Shimizu, R.,Ueda, S.,Shinya, S.,Kigawa, T.,Fukamizo, T.,Igarashi, M.,Utsumi, R.
Angucycline antibiotic waldiomycin recognizes common structural motif conserved in bacterial histidine kinases
J. Antibiot., 70:251-258, 2017

PubMed Abstract: Two-component signal transduction systems (TCSs), composed of a histidine kinase sensor (HK) and its cognate response regulator, sense and respond to environmental changes and are related to the virulence of pathogens. TCSs are potential targets for alternative antibiotics and anti-virulence agents. Here we found that waldiomycin, an angucycline antibiotic that inhibits a growth essential HK, WalK, in Gram-positive bacteria, also inhibits several class I HKs from the Gram-negative Escherichia coli. NMR analyses and site-directed mutagenesis studies using the osmo-sensing EnvZ, a prototypical HK of E. coli, showed that waldiomycin directly binds to both H-box and X-region, which are the two conserved regions in the dimerization-inducing and histidine-containing phosphotransfer (DHp) domain of HKs. Waldiomycin inhibits phosphorylation of the conserved histidine in the H-box. Analysis of waldiomycin derivatives suggests that the angucyclic ring, situated near the H-box in the waldiomycin-EnvZ DHp domain complex model, is responsible for the inhibitory activity. We demonstrate that waldiomycin is an HK inhibitor binding to the H-box region and has the potential of inhibiting a broad spectrum of HKs.

PubMed: 27999439
DOI: 10.1038/ja.2016.151

実験手法

X-RAY DIFFRACTION (2.3 Å)