FhuD: Difference between revisions
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<applet load='1esz' size=' | <applet load='1esz' size='400' frame='true' align='right' caption='Strucutre of the Periplasmic Ferric Siderophore Binding Protein FhuD complexed with Coprogen as determined by Clarke et al.' /> | ||
==OVERVIEW== | ==OVERVIEW== | ||
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==PROTEIN STRUCTURE== | ==PROTEIN STRUCTURE== | ||
FhuD structure is atypical for periplasmic ligand binding proteins. It is 266 residues in length containing a secondary structure composed of 41% helical (13 helices; 110 residues) and 17% beta sheet (13 strands; 47 residues). It is a bilobal kidney bean shape with approximate dimensions 60 Å ´ 30 Å ´ 40 Å.(ref both) containing two domains which are connected by a 23-residue kinked α-helix. The N-terminal domain (residues 27–141) twisted fived-stranded parallel β-sheet with 3-2-1-4-5 linking topology whereas the C-terminal domain (residues 166–288) has a mixed five stranded β-sheet 3-2-1-4-5 linking topology; both are enclosed by α-helices. Between the two domains lies the shallow siderophore binding site approximate 10 Å deep (REF) which forms depression or “pocket.” This pocket is lined with hydrophobic residues which side chain residues are able to create stabilizing hydrogen bond with the accepted siderophore. This is large enough to accommodate the hydrophobic orinthyl linkers of the siderophore. Through rearrangements of the residues of the binding pocket and interactions with the iron-hydroxamate centers of the siderophore, recognition can occur with structurally diverse siderophores. The binding diversity is further increased since the siderophore backbones do not interact with the proteins. | FhuD structure is atypical for periplasmic ligand binding proteins. It is 266 residues in length containing a secondary structure composed of 41% helical (13 helices; 110 residues) and 17% beta sheet (13 strands; 47 residues). It is a bilobal kidney bean shape with approximate dimensions 60 Å ´ 30 Å ´ 40 Å.(ref both) containing two domains which are connected by a 23-residue kinked α-helix. The N-terminal domain (residues 27–141) twisted fived-stranded parallel β-sheet with 3-2-1-4-5 linking topology whereas the C-terminal domain (residues 166–288) has a mixed five stranded β-sheet 3-2-1-4-5 linking topology; both are enclosed by α-helices. Between the two domains lies the shallow siderophore binding site approximate 10 Å deep (REF) which forms depression or “pocket.” This pocket is lined with hydrophobic residues which side chain residues are able to create stabilizing hydrogen bond with the accepted siderophore. This is large enough to accommodate the hydrophobic orinthyl linkers of the siderophore. Through rearrangements of the residues of the binding pocket and interactions with the iron-hydroxamate centers of the siderophore, recognition can occur with structurally diverse siderophores. The binding diversity is further increased since the siderophore backbones do not interact with the proteins. | ||
==PROTEIN FUNCTION== | ==PROTEIN FUNCTION== | ||
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. | |||
==INTERESTING CHARACTERS== | |||
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 conformational changes. 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) | [[User:Leni Rose|Leni Rose]] 04:57, 13 March 2010 (IST) | ||