Disease relevance of N-[3-[5,8-bis[3-(acetyl-oxido-amino)propyl]-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]propyl]-N-oxido-acetamide

• FhuA protein facilitates ligand-gated transport of ferrichrome-bound iron across Escherichia coli outer membranes [1].
• We exploited phage display to map protein-protein interactions in the E. coli cell envelope that contribute to ferrichrome transport [2].
• Three additional ferrichrome receptors were cloned from Pantoea agglomerans (formerly Erwinia herbicola), Salmonella paratyphi B and Salmonella typhimurium [3].
• A Yersinia enterocolitica receptor mutant was isolated which is impaired in ferrichrome uptake [3].
• fhuA of Actinobacillus pleuropneumoniae encodes a ferrichrome receptor but is not regulated by iron [4].

Psychiatry related information on N-[3-[5,8-bis[3-(acetyl-oxido-amino)propyl]-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]propyl]-N-oxido-acetamide

• A reaction time of 30 min and a pH of 3.9 gave an exchange yield of 27 and 83% for ferrichrysin and ferrichrome, respectively [5].

High impact information on N-[3-[5,8-bis[3-(acetyl-oxido-amino)propyl]-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]propyl]-N-oxido-acetamide

• The binding site of ferrichrome, an aromatic pocket near the cell surface, undergoes minor changes upon association with the ligand [1].
• FhuA, the receptor for ferrichrome-iron in Escherichia coli, is a member of a family of integral outer membrane proteins, which, together with the energy-transducing protein TonB, mediate the active transport of ferric siderophores across the outer membrane of Gram-negative bacteria [6].
• Upon binding of ferrichrome-iron, conformational changes are transduced to the periplasmic pocket of FhuA, signaling the ligand-loaded status of the receptor [6].
• A receptor domain controls the intracellular sorting of the ferrichrome transporter, ARN1 [7].
• Mutations within this domain lead to loss of ferrichrome binding and uptake activities and missorting of Arn1p, including a failure to relocalize to the plasma membrane in the presence of ferrichrome [7].

Chemical compound and disease context of N-[3-[5,8-bis[3-(acetyl-oxido-amino)propyl]-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]propyl]-N-oxido-acetamide

• Unlike OmpF and other E. coli porins, however, delta RV proteoliposomes transported stachyose (666 Da) and ferrichrome (740 Da) [8].
• FhuA in the outer membrane of Escherichia coli serves as a transporter for ferrichrome, the antibiotics albomycin and rifamycin CGP4832, colicin M, and as receptor for phages T1, T5 and phi80 [9].
• Using a growth promotion test, it was found that fit was not able to transport enterobactin, ferrichrome, transferrin, and lactoferrin in E. coli [10].
• One of the heme utilization mutants, DHH1, was found to be defective also in utilization of vibriobactin and ferrichrome, mimicking the Escherichia coli TonB- phenotype [11].
• Nucleotide sequence analysis of S. typhimurium and S. typhi chromosomal sequences flanking the ferrichrome operon identified a novel S. typhimurium fimbrial operon with a high level of similarity to sequences encoding Proteus mirabilis mannose-resistant fimbriae [12].

Biological context of N-[3-[5,8-bis[3-(acetyl-oxido-amino)propyl]-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]propyl]-N-oxido-acetamide

• Despite expression of Arn1p on the plasma membrane, mutant strains with defects in endocytosis exhibit reduced uptake of ferrichrome-iron [13].
• 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 [14].
• Since the structure of anguibactin differs strongly from that of ferrichrome there seems to be no co-evolution of receptor structure and substrate specificity [3].
• FoxA shared 33% amino acid sequence homology with FhuA, the ferrichrome receptor of Escherichia coli [15].
• A subtracted genomic fragment derived from the ferrichrome operon also hybridized to the intramacrophage cDNA [12].

Anatomical context of N-[3-[5,8-bis[3-(acetyl-oxido-amino)propyl]-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]propyl]-N-oxido-acetamide

• When cells are exposed to ferrichrome at low concentrations, Arn1p stably relocalizes to the plasma membrane [13].
• At higher concentrations of ferrichrome, Arn1p cycles between the plasma membrane and endosome [7].
• Tracer studies using (14)C-labeled ferrichrome bound to either iron(III) or aluminum(III), a nonreducible ligand for ferrichrome, indicate that ferrichrome enters the cell as the intact metallosiderophore and accumulates in the cytosol [16].
• All antibodies which could in this manner discriminate between FhuA and FhuA bound to ferrichrome had their determinants within a loop which is toward the N-terminus and which is exposed to the periplasm [17].
• tonB-independent ferrichrome-mediated iron transport in Escherichia coli spheroplasts [18].

Associations of N-[3-[5,8-bis[3-(acetyl-oxido-amino)propyl]-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]propyl]-N-oxido-acetamide with other chemical compounds

• Mutation of phenylalanine residues in the cytosolic tail of Arn1p also lead to missorting, but without defects in ferrichrome binding [7].
• Ustilago maydis secretes ferrichrome-type siderophores, ferric-ion-binding compounds, in response to iron starvation [19].
• Fre3p was required for the reduction and uptake of ferrioxamine B-iron and for growth on ferrioxamine B, ferrichrome, triacetylfusarinine C, and rhodotorulic acid in the absence of Fre1p and Fre2p [20].
• Peptide hydrogen bonding. Conformation dependence of the carbonyl carbon-13 nuclear magnetic resonance chemical shifts in ferrichrome. A study by 13C-[15N] Fourier double resonance spectroscopy1a [21].
• Results from trypsin digestion were interpreted as a conformational change in FhuA which had occurred upon ferrichrome binding, thereby preventing access of trypsin to lysine 67 [17].

Gene context of N-[3-[5,8-bis[3-(acetyl-oxido-amino)propyl]-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]propyl]-N-oxido-acetamide

• Aft1p activation in FIT-deleted strains occurred when either ferrichrome or ferric salts were used as sources of iron during growth, suggesting that the FIT genes enhance uptake of iron from both sources [22].
• Heterologous expression of SIT1 in the yeast Saccharomyces cerevisiae confirmed the function of Sit1p as a transporter for ferrichrome-type siderophores [23].
• The ferrichrome-iron receptor of Escherichia coli K-12 encoded by the fhuA gene is a multifunctional outer membrane receptor with an Mr of 78,000 [24].
• The tonB mutant was also defective in citrate-, ferrichrome-, and rhodoturulic acid-mediated iron uptake [25].
• Pulse-chase experiments with radiolabeled ferrichrome revealed release of ferrichrome from exbB, tonB, and fhuC mutants, showing that ferrichrome had not crossed the cytoplasmic membrane [26].

Analytical, diagnostic and therapeutic context of N-[3-[5,8-bis[3-(acetyl-oxido-amino)propyl]-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]propyl]-N-oxido-acetamide

• Most of these compounds, as identified by 1H and 13C nuclear magnetic resonance spectroscopy and X-ray crystallography, belong to the ferrichrome family [27].
• Molecular cloning of the ferrichrome-iron receptor of Escherichia coli K-12 [28].
• This bioassay has been used to demonstrate the structure-activity relationships of ferrichrome and several water-soluble hydroxamate peptide building blocks of this natural siderophore [29].
• Cells were separated from residual, soluble, radiolabeled ferrichrome by centrifugation in a micro-test tube containing three layers of nonmixable solutions of different densities [30].
• Ferrioxamine B and ferrichrome seemed to accumulate in an endosomal compartment, as shown by biochemical studies and by confocal microscopy study of cells loaded with a fluorescent derivative of ferrichrome [31].

References