Lactoferrins

Lactoferrin (from human whey). Purified by direct adsorption on cellulose phosphate by batch extraction, then eluted by a stepped salt and pH gradient. [Foley and Bates Anal Biochem 162 296 1987.]... 

Aguas, A., Esaguy, N., Sunkel, C.E., Silva, M.T. (1990). Cross-reactivity and sequence homology between the 65 kilodalton mycobacterial heat shock protein and human lactoferrin, transferrin, and DR beta subsets of major histocompatibility complex class II molecules. Infect. Immun. 58, 1461-1470. 

Lactoferrin j Iron-binding protein May inhibit growth of certain bacteria by binding iron and may be involved in regulation of proliferation of myeloid cells... 

Gutteridge, J.M.C. (1987). Bleomycin-detectable iron in knee-joint synovial fluid from arthritic patients and its relationship to the extracellular activities of caeruloplasmin, transferrin and lactoferrin. Biochem. J. 245, 415-421. 

Monteiro, H.P. and Winterbourne, C.C. (1988). The superoxide-dependent transfer of iron from ferritin to transferrin and lactoferrin. Biochem. J. 256, 923-928. 

Lactoferrin resembles transferrin in terms of molecular weight, amino-acid sequence homology and number of Fe(lII) binding sites. Lactoferrin is released from activated PMNs upon degranulation and may play a role in myelopoiesis, primary antibody response, lymphocyte proliferation, cytokine production and complement activation. 

Aruoma, 0.1. and Halliwell, B. (1987). Superoxide-dependent and ascorbate-dependent formation of hydroxyl radicals from hydrogen peroxide in the presence of iron. Are lactoferrin and transferrin promoters of hydroxyl radical generation. Biochem. J. 241, 273-278. 

Geborek, P., Mansson, B., Hellmer, G. and Saxne, T. (1992). Cytidine deaminase and lactoferrin in inflammatory synovial fluids - indicators of local polymorphonuclear cell function. Br. J. Rheumatol. 31, 235-240. 

Iron is, as part of several proteins, such as hemoglobin, essential for vertebrates. The element is not available as ion but mostly as the protein ligands transferrin (transport), lactoferrin (milk), and ferritin (storage), and cytochromes (electron transport) (Alexander 1994). Toxicity due to excessive iron absorption caused by genetic abnormalities exists. For the determination of serum Fe a spectrophoto-metric reference procedure exists. Urine Fe can be determined by graphite furnace (GF)-AAS, and tissue iron by GF-AAS and SS-AAS (Alexander 1994 Herber 1994a). Total Iron Binding Capacity is determined by fuUy saturated transferrin with Fe(III), but is nowadays mostly replaced by immunochemical determination of transferrin and ferritin. 

In a similar fashion, polyethylene glycol can be activated with CDI for connection to a protein, as has been shown for superoxide dismutase, a2-macroglobulin, a2-macro-globulin-trypsin, lactoferrin, and tissue plasminogen activator t208] [209]... 

Iron transport agents may belong to the protein or non-protein class. In the former group are found the animal proteins transferrin (25), lactoferrin (26) and conalbumin (27). The low molecular weight iron carrying compounds from microorganisms, the siderochromes, may occur with or without a bound metal ion. Typically, severe repression of biosynthesis of these substances can be expected to set in at an iron concentration of ca. 2 x 10-5 g atoms/liter (28). Most, but not all, of these substances can be described as phenolates or hydroxamates (4). 

Fig. 9. Comparison of FTIR absorption spectra of four proteins in H20 (left, amide I + II) and D20 (right, amide F + IF). Comparison between protein spectra for dominant secondary structure contributions from a-helix (myoglobin, MYO, top), /Fsheet (immunoglobin, IMUN), from both helix and sheet (lactoferrin, LCF) and from no long-range order (o -casein, CAS, bottom). The comparisons emphasize the high similarity, differing mostly by small frequency shifts of the amide I with the changes in secondary structure.

Figures 9 and 10 represent a selected comparison of amide V and I+II FTIR and VCD for four proteins in D2O solution. Of these, myoglobin (MYO) has a very high fraction of a-helix, immunoglobulin (IMU) has substantial /1-sheet component, lactoferrin (LAF) has both a and j3 contributions, and a-casein (CAS) supposedly has no extended structure. The FTIR spectra of these proteins change little, the primary difference...

Van Berkel, P.H., Welling, M.M., Geerts, M. et al. (2002) Large scale production of recombinant human lactoferrin in the milk of transgenic cows. Nature Biotechnology, 20 (5), 484—487. 

Figure 5.5 Stereo view of the Fe3+ binding site of (a) hFBP (b) human lactoferrin, N-lobe and (c) human transferrin (N-lobe). From Bruns, 1997. Reproduced by permission of Nature Publishing Group. 

FhuA and FepA will prove to be the reference structures for a large group of bacterial outer-membrane transporters that take up bacterial Fe3+-siderophores, Fe3+ released from host transferrin and lactoferrin, haem, and haem released from haemoglobin and haemopexin. It is assumed that all iron sources are transported... 

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. 

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