5NEC

Crystal structure of the siderophore receptor PiuD from Pseudomonas aeruginosa

5NEC の概要

• エントリーDOI: 10.2210/pdb5nec/pdb
• 分子名称: TonB-dependent siderophore receptor, (HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE (3 entities in total)
• 機能のキーワード: piud, outer membrane receptor, membrane protein
• 由来する生物種: Pseudomonas aeruginosa 39016
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 163622.64

構造登録者

Moynie, L.,Naismith, J.H. (登録日: 2017-03-10, 公開日: 2018-02-07, 最終更新日: 2024-11-06)

主引用文献

Luscher, A.,Moynie, L.,Auguste, P.S.,Bumann, D.,Mazza, L.,Pletzer, D.,Naismith, J.H.,Kohler, T.
TonB-Dependent Receptor Repertoire of Pseudomonas aeruginosa for Uptake of Siderophore-Drug Conjugates.
Antimicrob. Agents Chemother., 62:-, 2018

PubMed Abstract: The conjugation of siderophores to antimicrobial molecules is an attractive strategy to overcome the low outer membrane permeability of Gram-negative bacteria. In this Trojan horse approach, the transport of drug conjugates is redirected via TonB-dependent receptors (TBDR), which are involved in the uptake of essential nutrients, including iron. Previous reports have demonstrated the involvement of the TBDRs PiuA and PirA from and their orthologues in in the uptake of siderophore-beta-lactam drug conjugates. By screening, we further identified a PiuA orthologue, termed PiuD, present in clinical isolates, including strain LESB58. The gene in LESB58 is located at the same genetic locus as in strain PAO1. PiuD has a similar crystal structure as PiuA and is involved in the transport of the siderophore-drug conjugates BAL30072, MC-1, and cefiderocol in strain LESB58. To screen for additional siderophore-drug uptake systems, we overexpressed 28 of the 34 TBDRs of strain PAO1 and identified PfuA, OptE, OptJ, and the pyochelin receptor FptA as novel TBDRs conferring increased susceptibility to siderophore-drug conjugates. The existence of a TBDR repertoire in able to transport siderophore-drug molecules potentially decreases the likelihood of resistance emergence during therapy.

PubMed: 29555629
DOI: 10.1128/AAC.00097-18

実験手法

X-RAY DIFFRACTION (2.3 Å)