5NEC

Crystal structure of the siderophore receptor PiuD from Pseudomonas aeruginosa

Summary for 5NEC

• Entry DOI: 10.2210/pdb5nec/pdb
• Descriptor: TonB-dependent siderophore receptor, (HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE (3 entities in total)
• Functional Keywords: piud, outer membrane receptor, membrane protein
• Biological source: Pseudomonas aeruginosa 39016
• Total number of polymer chains: 2
• Total formula weight: 163622.64

Authors

Moynie, L.,Naismith, J.H. (deposition date: 2017-03-10, release date: 2018-02-07, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)