Selenium is an important nutrient. The lack of selenium will suppress expression of various enzymes that will lead to cell abnormality and diseases. However, high concentrations of free selenium are toxic to the cell because it adversely affects numerous cell metabolic pathways. In Methanococcus vannielii, selenium transport in the cell is established by the selenium-binding protein, SeBP. SeBP sequesters selenium during transport, thus regulating the level of free selenium in the cell, and delivers it specifically to the selenophosphate synthase enzyme. In solution, SeBP is an oligomer of 8.8-kDa subunits. It is a symmetric pentamer. The solution structure of SeBP was determined by NMR spectroscopy. Each subunit of SeBP is composed of an alpha-helix on top of a 4-stranded twisted beta-sheet. The stability of the five subunits stems mainly from hydrophobic interactions and supplemented by hydrogen bond interactions. The loop containing Cys(59) has been shown to be important for selenium binding, is flexible, and adopts multiple conformations. However, the cysteine accessibility is restricted in the structure, reducing the possibility of the binding of free selenium readily. Therefore, a different selenium precursor or other factors might be needed to facilitate opening of this loop to expose Cys(59) for selenium binding.
"However, high concentrations of free selenium are toxic to the cell because it adversely affects numerous cell metabolic pathways . Considering the toxicity of selenium, a specific transport carrier is needed to preserve the physical state of the selenium during the transport . "
[Show abstract][Hide abstract] ABSTRACT: The reduced expression of human selenium binding protein-1 (SELENBP1) has been reported for some human cancers. In this work we have estimated a reduced SELENBP1 expression by immunohistochemistry for the first time also in liver tissues of patients with hepatocarcinoma (HCC). Since the structure-function relationships of SELENBP1 are unknown, we have performed computational and experimental studies to have insight on the structural features of this protein focusing our attention on the properties of cysteines to assess their ability to interact with selenium. We have performed CD studies on the purified protein, modeled its three-dimensional structure, studied the energetic stability of the protein by molecular dynamics simulations, and titrated the cysteines by DTNB (5,5'-dithiobis (2-nitrobenzoic acid). The secondary structure content evaluated by CD has been found similar to that of 3D model. Our studies demonstrate that (i) SELENBP1 is an alpha-beta protein with some loop regions characterized by the presence of intrinsically unordered segments, (ii) only one cysteine (Cys57) is enough exposed to solvent, located on a loop and surrounded by charged and hydrophobic residues, and can be the cysteine able to bind the selenium. Furthermore, during the molecular dynamics simulation at neutral pH the loop containing Cys57 opens and exposes this residue to solvent, confirming that it is the best candidate to bind the selenium. Experimentally we found that only one cysteine is titratable by DTNB. This supports the hypothesis that Cys57 is a residue functionally important and this may open new pharmacological perspectives.
[Show abstract][Hide abstract] ABSTRACT: Investigations of transport phenomena have shown that the lattice part of thermal-conductivity of novel (TlBiS<sub>2</sub>)<sub>1-x</sub>(2PbS)<sub>x</sub> thermoelectrics decreases down to 0.26 W/mK, which is approaching the theoretical minimum. As a result, the thermoelectric figure of merit Z for these alloys ∼25% exceeding the respective value for lead sulfide at room temperature.
Semiconductor Conference, 2003. CAS 2003. International; 01/2003
[Show abstract][Hide abstract] ABSTRACT: The molecular details of the selenium metabolism and transport in living systems are still not completely understood, despite their physiological importance. Specifically, little is known about the membrane transport of selenium from most of the selenium containing compounds. In the present study, we investigated the mechanism for the membrane transport of selenium from red blood cells (RBCs) to the blood plasma. When the selenium distribution in the RBC ghost membrane after treatment with selenious acid was analyzed, nearly 70% of the selenium in the membrane was found to bind to the anion exchanger 1 (AE1) protein, which suggested that the integral protein AE1 is responsible for the membrane transport of selenium. The thiol dependency of the selenium export from the RBC to the blood plasma was examined using membrane permeable thiol reagents, i.e., N-ethylmaleimide (NEM) and tetrathionate (TTN). Treatment of the RBC with NEM, a thiol-alkylating reagent, resulted in modification of the thiol groups in the amino-terminal cytoplasmic domain (N-CPD) of the AE1, but not those in the membrane domain. Such an NEM treatment provided a marked inhibition of the selenium export from the RBC to the blood plasma. In addition, the treatment with TTN, a thiol-oxidizing reagent that forms intermolecular disulfide bonds, appeared to oxidize thiol groups in both the N-CPD and the membrane domain of AE1, which resulted in complete inhibition of the selenium export even during the initial period in which the export had a maximum velocity when using the thiol reagent-free treatment. Such complete inhibition of the selenium export from the TTN-treated RBC appeared to be due to the oligomerized AE1 proteins resulting from the intermolecularly formed disulfide bonds. These inhibitory effects using NEM and TTN suggested that thiol groups in the integral protein AE1 play essential roles in the membrane transport of the selenium from the RBCs to the blood plasma.
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