6BQS

HusA haemophore from Porphyromonas gingivalis

6BQS の概要

• エントリーDOI: 10.2210/pdb6bqs/pdb
• 関連するPDBエントリー: 6CRL
• NMR情報: BMRB: 27313
• 分子名称: hypothetical protein PG_2227 (1 entity in total)
• 機能のキーワード: haem binding protein, heme binding protein
• 由来する生物種: Porphyromonas gingivalis W83
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21745.51

構造登録者

Gell, D.A.,Kwan, A.H.,Horne, J.,Hugrass, B.M.,Collins, D.A.T. (登録日: 2017-11-28, 公開日: 2018-10-10, 最終更新日: 2024-05-01)

主引用文献

Gao, J.L.,Kwan, A.H.,Yammine, A.,Zhou, X.,Trewhella, J.,Hugrass, B.M.,Collins, D.A.T.,Horne, J.,Ye, P.,Harty, D.,Nguyen, K.A.,Gell, D.A.,Hunter, N.
Structural properties of a haemophore facilitate targeted elimination of the pathogen Porphyromonas gingivalis.
Nat Commun, 9:4097-4097, 2018

PubMed Abstract: Porphyromonas gingivalis is a keystone bacterial pathogen of chronic periodontitis. P. gingivalis is unable to synthesise the porphyrin macrocycle and relies on exogenous porphyrin, including haem or haem biosynthesis intermediates from host sources. We show that under the iron-limited conditions prevailing in tissue environments, P. gingivalis expresses a haemophore-like protein, HusA, to mediate the uptake of essential porphyrin and support pathogen survival within epithelial cells. The structure of HusA, together with titration studies, mutagenesis and in silico docking, show that haem binds in a hydrophobic groove on the α-helical structure without the typical iron coordination seen in other haemophores. This mode of interaction allows HusA to bind to a variety of abiotic and metal-free porphyrins with higher affinities than to haem. We exploit this unusual porphyrin-binding activity of HusA to target a prototypic deuteroporphyrin-metronidazole conjugate with restricted antimicrobial specificity in a Trojan horse strategy that effectively kills intracellular P. gingivalis.

PubMed: 30291238
DOI: 10.1038/s41467-018-06470-0

実験手法

SOLUTION NMR