Ferrichromes

Ferrichromes Hydroxamic acid 3 Species of Aspergillus, Neuro-spora, Paecilomyces, Penicil-lium, Spicaria, Ustilago, Crypto-coccus, Actinomyces, Sireptomy-ces and probably Sphacelotheca... 

Figure 3.3 Comparison of the FepA and FhuA crystal structures. A portion of the 13-barrel (in violet is removed to show the globular cork domain (in yellow) that inserts from the periplasm into the channel of the 11-barrel. FhuA is loaded with ferrichrome (iron is shown as a green ball) (Ferguson et ah, 1998 Locher et ah, 1998). The FepA crystal structure does not reveal Fe3+-enterobactin, but the FepA structure shown might be partially occupied by enterobactin (Buchanan et ah, 1999). 

Figure 3.5 Structures of FhuA ligands as determined by X-ray analysis of co-crystals with FhuA. Albomycin adopts an extended and a compact conformation in the FhuA crystal, and rifamycin CGP 4832 binds to the same FhuA site as ferrichrome and albomycin although it assumes a different conformation.

Figure 3.2 Chemical structures of selected siderophores to demonstrate the four major structural classes and the different solutions of microorganisms to scavenge iron. See for comparison the conformations of the Fe3+-complexes of ferrichrome and albomycin shown in Figure 3.5.

FhuA-mediated Ferrichrome Transport Across the Outer Membrane of . coli... 

Mainly the outer membrane ferrichrome receptor and transporter FhuA will be discussed because most structural and functional studies have been performed with this protein. In fact, FhuA was the first outer membrane protein identified (called TonA), with known functions as a phage and colicin receptor, that are related to iron transport (for a historical account, see Braun and Hantke 1977). 

The crystal structure of FhuA, with and without bound ferrichrome, has been determined (Ferguson et ah, 1998 Locher et al, 1998). FhuA consists of 22 antiparallel transmembrane 3-strands extending from residue 161 to residue 723, which form a (3-barrel (Figure 3.3, Plate 4). The -barrel strands are interconnected by large loops at the cell surface and small turns in the periplasm. Such a 3-barrel structure is the... 

Figure 3.6 Comparison of the chemical structures of rifamycin (Rifampicin ) and rifamycin CGP 4832 the latter is transported by FhuA. Note the entirely different chemical structures (Figure 3.2) and conformations (Figure 3.5) of the ferrichrome and albomycin FhuA transport substrates.

In the ferrichrome transport system (Figure 3.4), FhuD is the periplasmic ferrichrome binding protein, FhuB is the intrinsic cytoplasmic membrane protein, which probably evolved by fusion of two genes, and FhuC is the cytoplasmic... 

Escherichia coli FhuA FhuD FhuB FhuC Ferrichrome ... 

Bacillus subtilis Not applicable FhuD FhuB, FhuG FhuC Ferrichrome Schneider and Hantke,... 

The majority of Fur-regulated gene products are involved in iron uptake. Genes for transport and biosynthesis of enterobactin have been studied in E. coli K-12 (Earhart, 1996). It is assumed that this system is found in nearly every E. coli strain. Also the ferrichrome transport system seems to have a very broad distribution. The ferric citrate transport system (fee), however, is only present in some E. coli strains and may be part of a pathogenicity island. The aerobactin and yersiniabactin biosynthesis and transport systems are not found in all E. coli strains and are integrated into pathogenicity islands (Schubert et al., 1999). The ability to utilize haem seems also to be a specific pathogenicity-related adaptation. Haem transport systems are used in the animal or human host, where transferrin and lactoferrin create an iron-poor environment for bacteria. 

Another factor that relates complex stability and siderophore architecture is the chelate effect. The chelate effect is represented by an increase in complex stability for a multidentate ligand when compared to complexes with homologous donor atoms of lower denticity. The effect can be observed when comparing the stability of complexes of mono-hydroxamate ligands to their tris-hydroxamate analogs, such as ferrichrome (6) or desferrioxamine B (4). However, the increase in stability alone is not sufficient to explain the preponderance of hexadentate siderophores over tetradentate or bidentate siderophores in nature, and the chelate effect is not observed to a great extent in some siderophore structures (10,22,50,51). 

---