8RMI

Crystal structure of ferrioxamine transporter FoxA

This is a non-PDB format compatible entry.

Summary for 8RMI

• Entry DOI: 10.2210/pdb8rmi/pdb
• Descriptor: Ferrioxamine receptor FoxA, octyl beta-D-glucopyranoside, [1-[2-[2-[2-[2-[2-(dipyridin-2-ylamino)ethanoylamino]ethoxy]ethoxy]ethoxy]ethyl]-1,2,3-triazol-4-yl]methyl ~{N}-[5-[[4-[5-[[4-[5-[ethanoyl(oxidanyl)amino]pentylamino]-4-oxidanylidene-butanoyl]-oxidanyl-amino]pentylamino]-4-oxidanylidene-butanoyl]-oxidanyl-amino]pentyl]carbamate, ... (9 entities in total)
• Functional Keywords: tonb-dependent transporter siderophore, membrane protein
• Biological source: Pseudomonas aeruginosa PAO1
• Total number of polymer chains: 1
• Total formula weight: 92480.58

Authors

Josts, I.,Tidow, H.,Mislin, G. (deposition date: 2024-01-06, release date: 2024-11-20)

Primary citation

Faucon, A.,Renault, J.,Josts, I.,Couchot, J.,Renaud, J.L.,Hoegy, F.,Plesiat, P.,Tidow, H.,Gaillard, S.,Mislin, G.L.A.
Synthesis and antibacterial properties under blue LED light of conjugates between the siderophore desferrioxamine B (DFOB) and an Iridium(III) complex.
Bioorg.Med.Chem., 112:117842-117842, 2024

PubMed Abstract: The decline of antibiotics efficacy worldwide has recently reached a critical point urging for the development of new strategies to regain upper hand on multidrug resistant bacterial strains. In this context, the raise of photodynamic therapy (PDT), initially based on organic photosensitizers (PS) and more recently on organometallic PS, offers promising perspectives. Many PS exert their biological effects through the generation of reactive oxygen species (ROS) able to freely diffuse into and to kill surrounding bacteria. Hijacking of the bacterial iron-uptake systems with siderophore-PS conjugates would specifically target pathogens. Here, we report the synthesis of unprecedented conjugates between the siderophore desferrioxamine B (DFOB) and an antibacterial iridium(III) PS. Redox properties of the new conjugates have been determined at excited states and compared to that of an antibacterial iridium PS previously reported by our groups. Tested on nosocomial pathogen Pseudomonas aeruginosa and other bacteria, these conjugates demonstrated significant inhibitory activity when activated with blue LED light. Ir(III) conjugate and iridium free DFOB-2,2'-dipyridylamine ligands were crystallized in complex with FoxA, the outer membrane transporter involved in DFOB uptake in P. aeruginosa and revealed details of the binding mode of these unprecedented conjugates.

PubMed: 39173538
DOI: 10.1016/j.bmc.2024.117842

Experimental method

X-RAY DIFFRACTION (2.48 Å)