FhuD: Difference between revisions

Siderophores function within both gram-positive and gram-negative bacteria to aid in the uptake of iron. They are low molecular weight (500-1000 Da) and can bind with association constraints as high as ten to the power of 50. Let us consider E. coli which produces one siderophore called enterobactin yet can still use many siderophores including hydroxamate type, catecholates type, and citrate. These siderophores require assisted entrance into bacterial cells through uptake systems. In gram negative bacteria, including E. coli, an ATP binding cassette type (ABC) is used which requires several proteins including an outer membrane receptor, periplasmic transport protein and inner membrane proteins. When considering the hydroxamate type siderophore receptors of E.coli, specific outer membrane siderophore binding proteins are used such as FhuA for ferrichrome. After transport in the periplasm, the periplasmic binding protein FhuD is required for the movement of all hydroxamate type siderophores to the cytoplasm and inner membrane proteins FhuB and FhuC. This system allows for distribution of iron to the cell as required by the bacterium.  

Unlike other periplasmic ligand binding protein (PLBP), FhuD does not have the characteristic fold of a bilobate domain connected by flexible β-strands at the base of the ligand binding pocket. This results in FhuD adopting a novel PLBP structure. As designated by its structure, FhuD binds hydroxamate siderophores into a primarily hydrophobic pocket allowing the assumption that both binding and release do not cause large scale opening/closing. However in the binding pocket, several major ligand binding side chains have been noted to various positions depending on the ligand bound. Due to the ability of siderophore binding uptake systems to allow such a diverse array of siderophore bound molecules, new bacterial growth inhibiting agents may be developed. These agents will be delivered into the bacteria as silent “Trojan Horses” by the bacteria’s own uptake system.   

[[User:Leni Rose|Leni Rose]] 04:57, 13 March 2010 (IST)