Discussion 2ece

There is no doubt that putative Selenium binding protein (SBP) is of interest in research due to its correlation with cancer prevalence. We have found that a lot is known about the mechanisms and overall biology of Selenoproteins, figure 1.1 and Figure 1.2 but little about the non-selenocysteine SBP. Results of this research on selenium binding protein structure, homology sequences, and the literature revealed some aspects about SBP that may help to infer its function. The literature carries vast information about its distribution at species, systemic, organ and tissue levels but little about its molecular function. In literature we have identified some proteins that have some highest homology to SBP like the Acetaminophen Binding Protein (APBP) that is known to be present in the liver and is associated with metabolism of drugs. There is supporting evidence showing that SBP is also found in the live, with evidence showing SBP found in the liver of mus musculus (house mouse). Unfortunately the structure of this protein was not found in the protein databases for structural comparison with our protein of interest. However, considering the homology and literature evidence, a new dimension of thought arises considering the function of SBP. It is important to note as well that reports by Ishida et al, 2002 reveals that SBP can be induced by Ah-receptor ligands which the majority of them are the xenobiotics. These findings therefore suggest that SBP carry a function similar to APBP that is toxicity eradication or avoidance of heavy metal elements accumulation. This idea is substantiated by the fact that APBP is highly correlated with hepatic necrosis in patients who have taken acetaminophen overdose (Ishida et al, 2002). Necrosis is a defensive mechanism that multi-cellular organisms employ to eradicate diseased tissue from normal tissue, in most cases the necrotic tissue will accumulate the toxic substance, which can be a metal element or a carcinogenic substance. In this sense, it is obvious that a mediating protein that will treat the toxic substance as a ligand is crucial so that it will concentrate it at the necrotic region.

Using the protein databases and structural prediction servers we have revealed that SBP is a soluble protein not a transmembrane protein Figure 2.3. This suggests that it has the potential to be used as a messenger protein and in this case as a selenium binding protein that can move freely in the cytosol. Experiments from mice have shown that selenium circulate in the erythrocytes though a mediating protein between the circulatory system and other tissues like ovaries, testes, mammary glands, kidneys and liver that selenium is found though true function is not yet determined. However, studies by Porat et al, 2000 on the Bovine brain cytosol showed that SBP has a significant transport activity of other proteins. They found that this protein is responsible for linking the soluble and non soluble proteins during membrane fusion and docking of proteins to their destinations from the Golgi apparatus. This ability of SBP gives it a possibility of being a mere leader of carrier proteins during protein transport, but the fact that its core function is to sequestrate Se not to exceed certain amounts should not be overlooked. Normal cellular functioning has certain physiological optimum conditions and Se is one of the elements with a narrow range or with detrimental effects when it is in excess, hence it was termed an overall toxic mineral (Birringer, M. et al, 2002.) One can consider SBP as a protective agent against excess Se that cannot be incorporated in selenocysteines, and the fact that it is involved with transport of proteins from the Golgi might be serving as a dispersal mechanism for Se to tissues that require the element.

SBP has been shown to be induced at mRNA level by aryl hydrocarbon (Ah) - receptor ligands like the pentachlorobiphenyl (PCB126) in addition to that it has been shown that prostate cancer has an increase of SBP mRNA which can be reversed by treatment with hydroxytestosterone. (Ishida et al, 2002). This data implies that selenium binding protein may be scheming with immune system in the combat against cancers but further research need to be carried out to validate this notion. However, the Dali results are in accordance with this notion as most of the structuraly related proteins to SBP are pretty much linked to normal function of the cell like the chromosome condensation regulators as well as the nucleoporins that function during apoptopsis of cancerous cells. ( http://compbio.chemistry.uq.edu.au/mediawiki/index.php/Functional_analysis_of_2eceFigure). It is now evident that highly controlled reseasrch on animal models need to be carried out to find out more about SBP.

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