Disease relevance of ECs0156

• The crystal structure of FhuD from Escherichia coli in complex with the ferrichrome homolog gallichrome has been determined at 1.9 ¿ resolution, the first structure of a periplasmic binding protein involved in the uptake of siderophores [1].
• By panning random phage libraries against TonB and against FhuD, we identified interaction surfaces on each of these two proteins [2].

High impact information on ECs0156

• The crystal structure of Escherichia coli BtuF, the protein that binds vitamin B12 and delivers it to the periplasmic surface of the ABC transporter BtuCD, reveals a bi-lobed fold resembling that of the ferrichrome binding protein FhuD [3].
• These observations led us to propose a novel mechanism in which TonB acts as a scaffold, directing FhuD to regions within the periplasm where it is poised to accept and deliver siderophore [2].
• Prior saturation of the siderophorebinding site of FhuD with ferricrocin did not alter affinity of TonB for FhuD [2].
• FhuD residue Thr-181, located within the siderophorebinding site and mapping to a predicted TonB-interaction surface, was mutated to cysteine [2].
• Structures of FhuD complexed with the antibiotic albomycin, the fungal siderophore coprogen and the drug Desferal have been determined at high resolution by x-ray crystallography [4].

Chemical compound and disease context of ECs0156

• The processing of FhuD in E. coli was inhibited by globomycin [5].

Biological context of ECs0156

• The structure of the ferric siderophore binding protein FhuD complexed with gallichrome [1].
• Binding to FhuD was supported by the exclusive resistance of FhuD to proteinase K in the presence of the transport active hydroxamates [6].
• Triggering of ATP hydrolysis by substrate-loaded FhuD may occur by physical interaction between FhuD and FhuC, which bind close to each other on loop 7 [7].
• The fhu cassette operon expressed in a chromosomal fhu deletion mutant enabled us to evaluate the transport activity of mutated FhuA, FhuC, FhuD or FhuB derivatives [8].

Anatomical context of ECs0156

• The transmembrane region may be part of a pore through which a portion of FhuD inserts into the cytoplasmic membrane during transport [7].
• The overexpressed FhuD protein appeared in two forms of 31 and 28 kDa and was released upon conversion of vegetative cells into spheroplasts, suggesting synthesis of FhuD as a precursor and export into the periplasm [9].

Associations of ECs0156 with chemical compounds

• About 10(4) ferrichrome molecules were bound to the FhuD protein of cells which overproduced plasmid-encoded FhuD [6].
• FhuD T181C was reacted with two thiol-specific fluorescent probes; addition of the siderophore ferricrocin quenched fluorescence emissions of these conjugates [2].
• The FhuD protein, which is synthesized as a precursor and exported through the cytoplasmic membrane, represents the periplasmic binding protein of the system, accepting as substrates a number of hydroxamate siderophores and the antibiotic albomycin [10].

Analytical, diagnostic and therapeutic context of ECs0156

• A number of these important residues were localized in conserved regions according to a multiple sequence alignment of E. coli FhuD with other BP's that transport siderophores, heme, and vitamin B12 [11].

References